Acquired noncompaction in Duchenne muscular dystrophy.

Acquired left ventricular hypertrabeculation/noncompaction (LVHT) is rare and has been described in patients with mitochondriopathy, Barth syndrome, and Becker muscular dystrophy. Here we report acquired LVHT in a 28-year-old man with Duchenne muscular dystrophy who required non-invasive, positive-pressure ventilation for muscular respiratory failure since age 16 years. Transthoracic echocardiography at age 22 years revealed enlarged left atrium and ventricle and reduced fractional shortening, but no LVHT. Transthoracic echocardiography at age 27 years revealed enlarged left atrium and ventricle, systolic dysfunction, mitral insufficiency, and, surprisingly, LVHT. The cause and pathomechanism of acquired LVHT in this patient remained speculative.

    Acquired left ventricular hypertrabeculation/noncompaction (LVHT)
    SYMPTOMS

 is rare and has been described in patients with

    mitochondriopathy
    DIAGNOSIS

,

    Barth syndrome
    DIAGNOSIS

, and

    Becker muscular dystrophy
    DIAGNOSIS

. Here we report

    acquired LVHT
    DIAGNOSIS

 in a

    28-year-old
    AGE

    man
    GENDER

 with

    Duchenne muscular dystrophy
    DIAGNOSIS

 who required

    non-invasive, positive-pressure ventilation
    MEDICATION

 for

    muscular respiratory failure
    SYMPTOMS

 since

    age 16 years
    AGE

.

    Transthoracic echocardiography
    PARACLINICAL

 at

    age 22 years
    AGE

 revealed

    enlarged left atrium and ventricle
    SYMPTOMS

 and

    reduced fractional shortening
    SYMPTOMS

, but

    no LVHT
    NEG_FINDINGS

.

    Transthoracic echocardiography
    PARACLINICAL

 at

    age 27 years
    AGE

 revealed

    enlarged left atrium and ventricle
    SYMPTOMS

,

    systolic dysfunction
    SYMPTOMS

,

    mitral insufficiency
    SYMPTOMS

, and, surprisingly,

    LVHT
    SYMPTOMS

. The cause and pathomechanism of

    acquired LVHT
    DIAGNOSIS

 in this patient remained speculative.

mitochondriopathy
Barth syndrome
Becker muscular dystrophy
acquired LVHT
Duchenne muscular dystrophy
acquired LVHT


Disruption of DMD and deletion of ACSL4 causing developmental delay, hypotonia, and multiple congenital anomalies.

We have studied a male patient with significant developmental delay, growth failure, hypotonia, girdle weakness, microcephaly, and multiple congenital anomalies including atrial (ASD) and ventricular (VSD) septal defects. Detailed cytogenetic and molecular analyses revealed three de novo X chromosome aberrations and a karyotype 46,Y,der(X)inv(X) (p11.4q11.2)inv(X)(q11.2q21.32 approximately q22.2)del(X)(q22.3q22.3) was determined. The three X chromosome aberrations in the patient include: a pericentric inversion (inv 1) that disrupted the Duchenne muscular dystrophy (DMD) gene, dystrophin, at Xp11.4; an Xq11.2q21.32 approximately q22.2 paracentric inversion (inv 2) putatively affecting no genes; and an interstitial deletion at Xq22.3 that results in functional nullisomy of several known genes, including a gene previously associated with X-linked nonsyndromic mental retardation, acyl-CoA synthetase long chain family member 4 (ACSL4). These findings suggest that the disruption of DMD and the absence of ACSL4 in the patient are responsible for neuromuscular disease and cognitive impairment.

We have studied a

    male
    GENDER

 patient with

    significant developmental delay
    SYMPTOMS

,

    growth failure
    SYMPTOMS

,

    hypotonia
    SYMPTOMS

,

    girdle weakness
    SYMPTOMS

,

    microcephaly
    SYMPTOMS

, and

    multiple congenital anomalies including atrial (ASD) and ventricular (VSD) septal defects
    SYMPTOMS

.

    Detailed cytogenetic and molecular analyses
    PARACLINICAL

 revealed

    three de novo X chromosome aberrations
    GENETICS

 and a

    karyotype 46,Y,der(X)inv(X) (p11.4q11.2)inv(X)(q11.2q21.32 approximately q22.2)del(X)(q22.3q22.3) was determined
    GENETICS

. The

    three X chromosome aberrations
    GENETICS

 in the patient include: a

    pericentric inversion (inv 1) that disrupted the Duchenne muscular dystrophy (DMD) gene, dystrophin, at Xp11.4; an Xq11.2q21.32 approximately q22.2 paracentric inversion (inv 2) putatively affecting no genes
    GENETICS

; and an

    interstitial deletion at Xq22.3 that results in functional nullisomy of several known genes, including a gene previously associated with X-linked nonsyndromic mental retardation
    GENETICS

,

    acyl-CoA synthetase long chain family member 4 (ACSL4)
    BIOCHEMICAL

. These findings suggest that the

    disruption of DMD
    GENETICS

 and the

    absence of ACSL4
    GENETICS

 in the patient are responsible for

    neuromuscular disease
    DIAGNOSIS

 and

    cognitive impairment
    SYMPTOMS

.


[Dilated cardiomyopathy and lipid-lowering drug muscle toxicity revealing late-onset Becker's disease].

The Becker's muscular dystrophy is a genetic myopathy due to mutations of the dystrophin gene, located in the Xp21 region, with a clinical expression usually occurring in young adults.

We report an atypical case of late onset Becker's muscular dystrophy diagnosed at the age of 57. The patient suffered from mild skeletal muscle involvement revealed by the use of statins and fibrates, associated with severe dilating cardiomyopathy. The DNA analysis showed a deletion of the exons 11-13 in the Xp21 gene.

The diagnostic of Becker's muscular dystrophy must be considered in all patients with persistently elevated CPK and/or primitive dilated cardiomyopathy, whatever the age of the patient.

The

    Becker's muscular dystrophy
    DIAGNOSIS

 is a

    genetic myopathy
    DIAGNOSIS

 due to

    mutations of the dystrophin gene, located in the Xp21 region
    GENETICS

, with a clinical expression usually occurring in

    young adults
    AGE

.

We report an atypical case of

    late onset Becker's muscular dystrophy
    DIAGNOSIS

 diagnosed at the

    age of 57
    AGE

. The patient suffered from

    mild skeletal muscle involvement
    SYMPTOMS

 revealed by the

    use of statins and fibrates
    MEDICATION

, associated with

    severe dilating cardiomyopathy
    SYMPTOMS

. The

    DNA analysis
    PARACLINICAL

 showed a

    deletion of the exons 11-13 in the Xp21 gene
    GENETICS

.

The diagnostic of

    Becker's muscular dystrophy
    DIAGNOSIS

 must be considered in all patients with

    persistently elevated CPK
    BIOCHEMICAL

 and/or

    primitive dilated cardiomyopathy
    SYMPTOMS

, whatever the age of the patient.

Becker's muscular dystrophy
genetic myopathy
late onset Becker's muscular dystrophy
Becker's muscular dystrophy

mild skeletal muscle involvement
severe dilating cardiomyopathy
primitive dilated cardiomyopathy


Detection of a novel dystrophin gene mutation through carrier analysis performed during prenatal diagnosis in a case with intragenic recombination.

To report a multi-technical approach to Duchenne muscular dystrophy (DMD) mutation testing through carrier analysis, in the prenatal diagnosis of a male foetus without a known mutation segregating in the family and with inconclusive results of linkage analysis.

Haplotype analysis with the DMD region markers for assigning the carrier status of the mother and for prenatal diagnosis of foetal DNA; semiquantitative multiplex analysis of maternal and foetal DNA for the promoter and for 34 exons of the DMD gene; sequencing analysis of the maternal and foetal DNA for confirmation of the results.

Because of an intragenic recombination of the DMD gene in foetal DNA, haplotype analysis gave inconclusive results. Semiquantitative PCR analysis displayed a pattern compatible with a heterozygous exon 60 mutation in the mother's DNA, while foetal DNA showed a normal migration pattern. Sequencing analysis confirmed the presence of a novel 7 base-pair deletion in exon 60 of the DMD gene in the mother and excluded the deletion in the foetus.

Semiquantitative PCR results allowed the DMD mutation detection in the mother and the exclusion in the foetus, showing its crucial importance in prenatal diagnosis in those cases where linkage analysis is not conclusive.

To report a multi-technical approach to

    Duchenne muscular dystrophy (DMD) mutation testing
    DIAGNOSIS

 through

    carrier analysis
    PARACLINICAL

, in the

    prenatal diagnosis
    AGE

 of a

    male
    GENDER

    foetus without a known mutation segregating in the family
    AGE

 and with

    inconclusive results of linkage analysis
    NEG_FINDINGS

.

    Haplotype analysis with the DMD region markers
    PARACLINICAL

 for assigning the carrier status of the mother and for

    prenatal diagnosis of foetal DNA
    PARACLINICAL

;

    semiquantitative multiplex analysis of maternal and foetal DNA for the promoter and for 34 exons of the DMD gene
    PARACLINICAL

;

    sequencing analysis of the maternal and foetal DNA
    PARACLINICAL

 for confirmation of the results.

Because of an

    intragenic recombination of the DMD gene in foetal DNA
    GENETICS

,

    haplotype analysis gave inconclusive results
    NEG_FINDINGS

.

    Semiquantitative PCR analysis
    PARACLINICAL

 displayed a

    pattern compatible with a heterozygous exon 60 mutation in the mother's DNA
    GENETICS

, while foetal DNA showed a

    normal migration pattern
    NEG_FINDINGS

.

    Sequencing analysis
    PARACLINICAL

 confirmed the

    presence of a novel 7 base-pair deletion in exon 60 of the DMD gene in the mother
    GENETICS

 and

    excluded the deletion in the foetus
    FAMILY

.

    Semiquantitative PCR results
    PARACLINICAL

 allowed the

    DMD mutation detection in the mother and the exclusion in the foetus
    GENETICS

, showing its crucial importance in

    prenatal diagnosis
    PARACLINICAL

 in those cases where

    linkage analysis is not conclusive
    NEG_FINDINGS

.


Cardiac rehabilitation after heart transplantation in a patient with Becker's muscular dystrophy: a case report.

Becker's muscular dystrophy (BMD) is associated with abnormal cardiac findings in 75% of cases; up to one third will develop ventricular dilatation leading to congestive heart failure, at times necessitating cardiac transplant. Candidates are selected from a base of heart failure patients who are usually New York Heart Association (NYHA) class III or IV. Treatment in a phase II cardiac rehabilitation program after transplantation is associated with functional improvement in patients without BMD, but there are no reports of patients with this disorder. We present the case of a 38-year-old man diagnosed with BMD with associated dilated cardiomyopathy. The patient was a NYHA class IIIa and underwent orthotopic cardiac transplantation for intractable heart failure followed by treatment in a phase II cardiac rehabilitation program. At the end of cardiac rehabilitation, his 12-minute walking distance had improved from 716.28 to 929.64 m (30% improvement), he had increased his conditioning metabolic equivalent level from 3.5 to 5.5 (55% improvement), he had a weight loss from 81.65 to 78.93 kg, and his body mass index changed from 23 to 22 kg/m2. The patient now has returned to work, is using a stationary bicycle once a day for 30 minutes, and is walking 1 hour a day. This suggests that treatment in a cardiac rehabilitation program is effective in patients with BMD after cardiac transplant.

    Becker's muscular dystrophy (BMD)
    DIAGNOSIS

 is associated with

    abnormal cardiac findings
    SYMPTOMS

 in 75% of cases; up to one third will develop

    ventricular dilatation
    SYMPTOMS

 leading to

    congestive heart failure
    SYMPTOMS

, at times necessitating

    cardiac transplant
    MEDICATION

. Candidates are selected from a base of

    heart failure
    DIAGNOSIS

 patients who are usually

    New York Heart Association (NYHA) class III or IV
    SYMPTOMS

.

    Treatment in a phase II cardiac rehabilitation program
    MEDICATION

 after

    transplantation
    MEDICATION

 is associated with

    functional improvement
    SYMPTOMS

 in patients

    without BMD
    NEG_FINDINGS

, but there are no reports of patients with this disorder. We present the case of a

    38-year-old
    AGE

    man
    GENDER

 diagnosed with

    BMD
    DIAGNOSIS

 with associated

    dilated cardiomyopathy
    DIAGNOSIS

. The patient was a

    NYHA class IIIa
    DIAGNOSIS

 and underwent

    orthotopic cardiac transplantation
    MEDICATION

 for

    intractable heart failure
    DIAGNOSIS

 followed by

    treatment in a phase II cardiac rehabilitation program
    MEDICATION

. At the end of

    cardiac rehabilitation
    MEDICATION

, his

    12-minute walking distance had improved from 716.28 to 929.64 m (30% improvement
    SYMPTOMS

),

    he
    GENDER

 had

    increased his conditioning metabolic equivalent level from 3.5 to 5.5
    BIOCHEMICAL

    (55% improvement
    SYMPTOMS

),

    he
    GENDER

 had a

    weight loss from 81.65 to 78.93 kg
    SYMPTOMS

, and his

    body mass index changed from 23 to 22 kg/m2
    SYMPTOMS

. The patient now has returned to work, is

    using a stationary bicycle once a day for 30 minutes
    MEDICATION

, and is

    walking 1 hour a day
    MEDICATION

. This suggests that

    treatment in a cardiac rehabilitation program
    MEDICATION

 is effective in patients with

    BMD
    DIAGNOSIS

 after

    cardiac transplant
    MEDICATION

.

Becker's muscular dystrophy (BMD)
heart failure
BMD
dilated cardiomyopathy
NYHA class IIIa
intractable heart failure
BMD


[Respiratory muscle aids during an episode of aspiration in a patient with Duchenne muscular dystrophy].

We report the case of a Duchenne muscular dystrophy patient with good bulbar function but severely decreased forced vital capacity (9%) and spontaneous peak cough flow (PCF) (2.35 L/s). The patient needed continuous noninvasive ventilation (NIV) consisting of a volumetric ventilator with a nighttime nasal mask and a daytime mouthpiece. He also required application of manually assisted coughing techniques by insufflation with a resuscitation bag and chest thrust (manually assisted PCF after maximum insufflation capacity of 4.33 L/s). An episode of serious food aspiration was resolved by his main caregiver through NIV and manually assisted coughing. Bronchoscopy under sedation using NIV with a lip seal connection to his volumetric ventilator later revealed that no material remained. This case exemplifies the potential role of skilled respiratory management in some neuromuscular diseases.

We report the case of a

    Duchenne muscular dystrophy
    DIAGNOSIS

 patient with

    good bulbar function
    SYMPTOMS

 but

    severely decreased forced vital capacity (9%)
    SYMPTOMS

 and

    spontaneous peak cough flow (PCF) (2.35 L/s)
    SYMPTOMS

. The patient needed

    continuous noninvasive ventilation (NIV) consisting of a volumetric ventilator with a nighttime nasal mask and a daytime mouthpiece
    MEDICATION

.

    He
    GENDER

 also required

    application of manually assisted coughing techniques by insufflation with a resuscitation bag and chest thrust (manually assisted PCF after maximum insufflation capacity of 4.33 L/s)
    MEDICATION

. An

    episode of serious food aspiration
    SYMPTOMS

 was resolved by his main caregiver through

    NIV and manually assisted coughing
    MEDICATION

.

    Bronchoscopy under sedation using NIV with a lip seal connection to his volumetric ventilator
    PARACLINICAL

 later revealed that

    no material remained
    NEG_FINDINGS

. This case exemplifies the potential role of

    skilled respiratory management
    MEDICATION

 in some

    neuromuscular diseases
    DIAGNOSIS

.

Duchenne muscular dystrophy
neuromuscular diseases


CardioWest total artificial heart in a moribund adolescent with left ventricular thrombi.

Bridge to transplant is a well-known strategy to enable patients with congestive heart failure to live until transplant. A 15-year-old boy with Beckers' muscular dystrophy and cardiomyopathy was accepted for heart transplantation. He suffered a cardiac arrest and was placed on extracorporeal membrane oxygenator. A paracorporeal biventricular assist device and a total artificial heart were considered for bridge to transplant. A CardioWest total artificial heart was chosen because of the patient's size. Multiple left ventricular thrombi were identified at the time of the ventriculectomy. The patient did well with the total artificial heart was transplanted and discharged home. The unknown presence of significant left ventricular thrombi raises the question of outcome with a paracorporeal ventricular assist device.

    Bridge to transplant
    MEDICATION

 is a well-known strategy to enable patients with

    congestive heart failure
    DIAGNOSIS

 to

    live until transplant
    MEDICATION

. A

    15-year-old
    AGE

    boy
    GENDER

 with

    Beckers' muscular dystrophy
    DIAGNOSIS

 and

    cardiomyopathy
    DIAGNOSIS

 was accepted for

    heart transplantation
    MEDICATION

.

    He
    GENDER

 suffered a

    cardiac arrest
    SYMPTOMS

 and was

    placed on extracorporeal membrane oxygenator
    MEDICATION

. A

    paracorporeal biventricular assist device and a total artificial heart
    MEDICATION

 were considered for

    bridge to transplant
    MEDICATION

. A

    CardioWest total artificial heart
    MEDICATION

 was chosen because of the patient's size.

    Multiple left ventricular thrombi
    SYMPTOMS

 were identified at the time of the

    ventriculectomy
    MEDICATION

. The patient did well with the

    total artificial heart was transplanted
    MEDICATION

 and

    discharged home
    MEDICATION

. The

    unknown presence of significant left ventricular thrombi
    SYMPTOMS

 raises the question of outcome with a

    paracorporeal ventricular assist device
    MEDICATION

.

congestive heart failure
Beckers' muscular dystrophy
cardiomyopathy


Left ventricular synchronization by biventricular pacing in Becker muscular dystrophy as assessed by tissue Doppler imaging.

Biventricular (BiV) pacing is a promising therapy for severe heart failure. The effect of BiV pacing is cardiac resynchronization of both ventricles. Asynchrony of the ventricular contraction and restoration of cardiac synchronization can be assessed by tissue Doppler imaging. Here we describe a patient with Becker muscular dystrophy with heart failure caused by dilated cardiomyopathy in whom a BiV pacemaker was implanted.

    Biventricular (BiV) pacing
    MEDICATION

 is a promising therapy for

    severe heart failure
    DIAGNOSIS

. The effect of

    BiV pacing
    MEDICATION

 is

    cardiac resynchronization of both ventricles
    SYMPTOMS

.

    Asynchrony of the ventricular contraction
    SYMPTOMS

 and

    restoration of cardiac synchronization
    SYMPTOMS

 can be assessed by

    tissue Doppler imaging
    PARACLINICAL

. Here we describe a patient with

    Becker muscular dystrophy
    DIAGNOSIS

 with

    heart failure
    SYMPTOMS

 caused by

    dilated cardiomyopathy
    DIAGNOSIS

 in whom a

    BiV pacemaker was implanted
    MEDICATION

.

Biventricular (BiV) pacing
BiV pacing
BiV pacemaker was implanted

severe heart failure
Becker muscular dystrophy
dilated cardiomyopathy


A novel cryptic exon identified in the 3' region of intron 2 of the human dystrophin gene.

The dystrophin gene, which is mutated in Duchenne muscular dystrophy (DMD), is the largest known human gene and is characterized by the huge size of its introns. Intron 2, the second largest intron, is 170-kb long and has been shown to include a 140-bp cryptic exon (exon 2a) in its 5' region. The rest of this intron has no known function. In this study, we find that another cryptic exon, located in the 3' region of intron 2, is activated in a promoter- or tissue-specific manner. An unknown 98-bp insertion precisely between exons 2 and 3 was identified in one of the dystrophin mRNAs from lymphocytes of a DMD patient with a duplication of exon 2. This 98-bp sequence, located in the 3' region of intron 2, was found to possess a branch point, acceptor and donor splice-site consensus sequences, and an exonic splicing enhancer sequence, and thus is a novel exon, which we named "exon 2b." In lymphocytes, exon 2b incorporation was detected in the muscle-specific, promoter-driven transcript. Five of 20 normal human tissue mRNAs, including cardiac and skeletal muscle mRNAs, were confirmed to contain a fragment extending from exon 1 to exon 2b by reverse transcription PCR amplification, indicating that exon 2b is activated in a tissue-specific manner. This provides a clue to a novel cause of dystrophinopathy.

The

    dystrophin gene
    GENETICS

, which is mutated in

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

, is the largest known human gene and is characterized by the

    huge size of its introns
    GENETICS

.

    Intron 2, the second largest intron, is 170-kb long
    GENETICS

 and has been shown to include a

    140-bp cryptic exon (exon 2a) in its 5'
    GENETICS

 region. The rest of this intron has no known function. In this study, we find that another

    cryptic exon, located in the 3' region of intron 2
    GENETICS

, is activated in a

    promoter- or tissue-specific manner
    GENETICS

. An

    unknown 98-bp insertion precisely between exons 2 and 3
    GENETICS

 was identified in one of the

    dystrophin mRNAs
    GENETICS

 from lymphocytes of a

    DMD
    DIAGNOSIS

 patient with a

    duplication of exon 2
    GENETICS

. This

    98-bp sequence, located in the 3' region of intron 2, was found to possess a branch point, acceptor and donor splice-site consensus sequences, and an exonic splicing enhancer sequence, and thus is a novel exon,
    GENETICS

 which we named "exon 2b." In lymphocytes,

    exon 2b incorporation
    GENETICS

 was detected in the

    muscle-specific, promoter-driven transcript
    GENETICS

. Five of 20 normal human tissue mRNAs, including

    cardiac and skeletal muscle mRNAs
    MICROSCOPIC

, were confirmed to contain a fragment

    extending from exon 1 to exon 2b
    GENETICS

 by

    reverse transcription PCR amplification
    PARACLINICAL

, indicating that

    exon 2b
    GENETICS

 is activated in a tissue-specific manner. This provides a clue to a novel cause of

    dystrophinopathy
    DIAGNOSIS

.

Duchenne muscular dystrophy (DMD)
DMD
dystrophinopathy


Left ventricular hypertrabeculation/noncompaction as a cardiac manifestation of Duchenne muscular dystrophy under non-invasive positive-pressure ventilation.

Though cardiac involvement is a frequent finding in patients with Duchenne muscular dystrophy (DMD) at the wheel-chair-bound stage, left ventricular hypertrabeculation (LVHT) has not been reported. The patient is a 28-year-old male with the typical clinical features of end stage DMD. Since the age of 16 years he required ventilatory support by means of non-invasive positive-pressure ventilation (NIPPV), initially intermittently and since age 27 permanently. Since the age of 21 years he developed chronic heart failure, and since age 24 atrial flutter, successfully treated with amiodarone. After discontinuation of amiodarone because of hyperthyroidism, he developed atrial fibrillation. Echocardiography at age 28 revealed mitral insufficiency, enlarged left atrial diameter, and, surprisingly, LVHT. Since LVHT was absent at the initial echocardiographic examination, it was regarded acquired. The case shows that cardiac involvement in DMD may not only comprise rhythm abnormalities, valve abnormalities, and dilative cardiomyopathy, but also LVHT in single cases.

Though

    cardiac involvement
    SYMPTOMS

 is a frequent finding in patients with

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 at the

    wheel-chair-bound stage
    MEDICATION

,

    left ventricular hypertrabeculation (LVHT)
    SYMPTOMS

 has not been reported. The patient is a

    28-year-old
    AGE

    male
    GENDER

 with the typical clinical features of

    end stage DMD
    DIAGNOSIS

.

    Since the age of 16 years
    AGE

    he
    GENDER

 required

    ventilatory support by means of non-invasive positive-pressure ventilation (NIPPV), initially intermittently and since age 27 permanently
    MEDICATION

. Since the

    age of 21 years
    AGE

    he
    GENDER

 developed

    chronic heart failure
    SYMPTOMS

, and since

    age 24 atrial flutter
    AGE

, successfully treated with

    amiodarone
    MEDICATION

. After

    discontinuation of amiodarone
    MEDICATION

 because of

    hyperthyroidism
    SYMPTOMS

,

    he
    GENDER

 developed

    atrial fibrillation
    SYMPTOMS

.

    Echocardiography
    PARACLINICAL

 at

    age 28
    AGE

 revealed

    mitral insufficiency
    SYMPTOMS

,

    enlarged left atrial diameter
    SYMPTOMS

, and, surprisingly,

    LVHT
    SYMPTOMS

. Since

    LVHT was absent at the initial echocardiographic examination
    NEG_FINDINGS

, it was regarded acquired. The case shows that

    cardiac involvement
    SYMPTOMS

 in

    DMD
    DIAGNOSIS

 may not only comprise

    rhythm abnormalities
    SYMPTOMS

,

    valve abnormalities
    SYMPTOMS

, and

    dilative cardiomyopathy
    SYMPTOMS

, but also

    LVHT
    DIAGNOSIS

 in single cases.

Duchenne muscular dystrophy (DMD)
end stage DMD
DMD
LVHT


[Therapy of Duchenne muscular dystrophy with umbilical cord blood stem cell transplantation].

To analyze a Duchenne muscular dystrophy(DMD) patient's muscular regeneration, dystrophin expression and locomotive variation before and after he underwent umbilical cord blood stem cell transplantation in order to assess the therapeutic effect.

A 12-year-old DMD boy who could not walk for 3 years was confirmed by gene analysis and dystrophin protein immune test on his muscle. He had no other chronic disease. By HLA matching, a piece of umbilical cord blood stem cell with 6 HLA sites matching to the boy was found in Guangdong Umbilical Cord Blood Bank. The number of the nucleated cells of the umbilical cord blood stem cell was 24.08x 10(8). After pretreatment for the DMD boy with busulfan, cyclophosphamide and rabbit anti-human thymocyte globulin, the allergenic cord blood stem cells were transplanted into him by intravenous injection. Cyclosporin A, methylprednisolone, MMF, prostaglandin E1 and ganciclovir were given after the transplantation. At the same time, Gran, the granulocytic cell stimulating factor, and gamma globulin were administered. The biochemistry profile including serum creatine kinase (CK), the reconstruction of blood making, the deletion exon of DMD gene, the regenerating muscles, the dystrophin protein expression, and the locomotive function of the DMD boy were tested regularly.

(1) The white blood cells (WBC) of peripheral blood decreased gradually to zero after pretreatment. In a period of 15 days after transplantation, the neutrophil increased to 0.5x 10(9)/L; at 25 days, WBC increased to normal level. Blood platelet was more than 20x 10(9)/L at 22 days. The hemoglobin rose to 85-100 g/L. At 140 days, sternal puncture revealed the rapid growth of neutrophil, blood platelet and hemoglobin. (2)At 140 days, the blood type of the DMD boy transformed from type O to type AB (the donor's blood type being AB). There was no grafe versus host reaction. (3) At 18, 30, 43, 55, 74 and 233 days after transplantation, the PCR-short tandem repeat test of the boy's peripheral blood DNA showed that his genotype was completely the same as the donor's. The results of PCR-short tandem repeat tests of the bone marrow cells DNA by sternal puncture at 140, 183 and 235 days were the same as those of the blood DNA. (4) At 60 days, DMD gene analysis by PCR showed that the defected DMD gene (exon 19 deletion) had been corrected by the umbilical cord stem cells transplantation. (5) At 75 days, the biopsy of calf muscle showed there were myoblast cells and muscular tubes growing. The dystrophin expressions were weak, but a few of them were strong. DNA analysis showed that the donor's gene DNA accounted for 1%-13%. At 126 days, obviously increased dystrophin positive muscular fibers of the boy were found. The donor's fibers rose to 2.5%-25%. (6) The serum CK of the boy declined from 5735 U/L to 274 U/L. (7) At 100 days, physical examination revealed improvement in his arms and legs.

The therapy of Duchenne muscular dystrophy with allogeneic umbilical cord blood hematopoietic stem cell transplantation may reset up the blood-making function, decrease the serum CK level, restore the dystrophin in muscles, and improve the locomotive function of the DMD boy. These data suggest that the allogeneic umbilical cord blood hematopoietic stem cell transplantation may benefit the DMD boys.

To analyze a

    Duchenne muscular dystrophy(DMD)
    DIAGNOSIS

 patient's

    muscular regeneration
    SYMPTOMS

,

    dystrophin expression
    BIOCHEMICAL

 and

    locomotive variation
    SYMPTOMS

 before and after

    he
    GENDER

 underwent

    umbilical cord blood stem cell transplantation
    MEDICATION

 in order to assess the therapeutic effect.

A

    12-year-old
    AGE

    DMD
    DIAGNOSIS

    boy
    GENDER

 who

    could not walk for 3 years
    NEG_FINDINGS

 was confirmed by

    gene analysis
    PARACLINICAL

 and

    dystrophin protein immune test on his muscle
    PARACLINICAL

.

    He
    GENDER

 had

    no other chronic disease
    NEG_FINDINGS

. By

    HLA matching
    PARACLINICAL

, a

    piece of umbilical cord blood stem cell with
    MEDICATION

 6 HLA sites matching to the

    boy
    GENDER

 was found in Guangdong Umbilical Cord Blood Bank. The

    number of the nucleated cells of the umbilical cord blood stem cell was 24.08x 10(8)
    MICROSCOPIC

. After

    pretreatment for
    MEDICATION

 the

    DMD
    DIAGNOSIS

    boy
    GENDER

    with busulfan, cyclophosphamide and rabbit anti-human thymocyte globulin
    MEDICATION

,

    the allergenic cord blood stem cells were transplanted into him by intravenous injection
    MEDICATION

.

    Cyclosporin A, methylprednisolone, MMF, prostaglandin E1 and ganciclovir
    MEDICATION

 were given

    after the transplantation
    MEDICATION

. At the same time,

    Gran, the granulocytic cell stimulating factor, and gamma globulin
    MEDICATION

 were administered. The

    biochemistry profile including serum creatine kinase (CK)
    PARACLINICAL

,

    the reconstruction of blood making
    PARACLINICAL

, the

    deletion exon of DMD gene
    GENETICS

, the

    regenerating muscles
    SYMPTOMS

, the

    dystrophin protein expression
    BIOCHEMICAL

, and the

    locomotive function
    SYMPTOMS

 of the

    DMD
    DIAGNOSIS

    boy
    GENDER

 were tested regularly.

(1)

    The white blood cells (WBC) of peripheral blood decreased gradually to zero after pretreatment
    BIOCHEMICAL

. In a period of 15 days after

    transplantation
    MEDICATION

,

    the neutrophil increased to 0.5x 10(9)/L
    BIOCHEMICAL

; at 25 days,

    WBC increased to normal level
    BIOCHEMICAL

.

    Blood platelet was more than 20x 10(9)/L
    BIOCHEMICAL

 at 22 days. The hemoglobin rose to 85-100 g/L. At 140 days,

    sternal puncture
    PARACLINICAL

 revealed the

    rapid growth of neutrophil, blood platelet and hemoglobin
    BIOCHEMICAL

. (2)At 140 days, the blood type of the

    DMD
    DIAGNOSIS

    boy
    GENDER

    transformed from type O to type AB (the donor's blood type being AB)
    GENETICS

. There was

    no grafe versus host reaction
    NEG_FINDINGS

. (3) At 18, 30, 43, 55, 74 and 233 days after

    transplantation
    MEDICATION

, the

    PCR-short tandem repeat test of the boy
    PARACLINICAL

    's peripheral blood DNA
    PARACLINICAL

 showed that

    his
    GENDER

    genotype was completely the same as the donor's
    GENETICS

. The results of

    PCR-short tandem repeat tests of the bone marrow cells DNA by sternal puncture
    PARACLINICAL

 at 140, 183 and 235 days were the same as those

    of the blood DNA
    PARACLINICAL

. (4) At 60 days,

    DMD gene analysis by PCR
    PARACLINICAL

 showed that

    the defected DMD gene (exon 19 deletion) had been corrected
    GENETICS

 by the

    umbilical cord stem cells transplantation
    MEDICATION

. (5) At 75 days, the

    biopsy of calf muscle
    PARACLINICAL

 showed

    there were myoblast cells and muscular tubes growing
    MICROSCOPIC

. The

    dystrophin expressions were weak
    SYMPTOMS

, but a

    few of them were strong
    MICROSCOPIC

.

    DNA analysis
    PARACLINICAL

 showed that

    the donor's gene DNA accounted for 1%-13%
    GENETICS

. At 126 days,

    obviously increased dystrophin positive muscular fibers of the boy
    MICROSCOPIC

    were found
    MICROSCOPIC

.

    The donor's fibers rose to 2.5%-25%
    MICROSCOPIC

. (6) The

    serum CK of
    BIOCHEMICAL

 the

    boy
    GENDER

 declined from 5735 U/L to 274 U/L. (7) At 100 days,

    physical examination
    PARACLINICAL

 revealed

    improvement in his arms and legs
    SYMPTOMS

.

The therapy of

    Duchenne muscular dystrophy
    DIAGNOSIS

 with

    allogeneic umbilical cord blood hematopoietic stem cell transplantation
    MEDICATION

 may

    reset up the blood-making function
    BIOCHEMICAL

,

    decrease the serum CK level
    BIOCHEMICAL

,

    restore the dystrophin in muscles
    MICROSCOPIC

, and

    improve the locomotive function
    SYMPTOMS

 of the

    DMD
    DIAGNOSIS

    boy
    GENDER

. These data suggest that the

    allogeneic umbilical cord blood hematopoietic stem cell transplantation
    MEDICATION

 may benefit the

    DMD
    DIAGNOSIS

    boys
    GENDER

.

Duchenne muscular dystrophy(DMD)
DMD
DMD
DMD
DMD
Duchenne muscular dystrophy
DMD
DMD

muscular regeneration
locomotive variation
regenerating muscles
locomotive function
dystrophin expressions were weak
improvement in his arms and legs
improve the locomotive function

could not walk for 3 years
no other chronic disease
no grafe versus host reaction


Mutation spectrum leading to an attenuated phenotype in dystrophinopathies.

Although Becker muscular dystrophy (BMD; MIM 300376) is mainly caused by gross deletions of the dystrophin gene, the nature of the mutations involved in the remaining cases is of importance because of the milder clinical course of Becker. We have extensively characterized the mRNA changes associated with five novel point mutations giving rise to a Becker phenotype, which confirm that Becker arises largely due to alterations in splicing. In two cases the milder phenotype arises because of exon skipping, leading to an in-frame deletion (c.1603-2A>C and c.4250T>A). In further two cases intronic mutations (c.4519-5C>G and c.961-5925A>C) result in complex splicing changes, but with some residual normal transcripts. The last case, c.10412T>A (p.Leu3471X), results in a truncated transcript missing only part of the COOH terminal of the protein, suggesting that this region is not crucial for dystrophin function. The detection of a low amount of dystrophin in this patient could be attributable to a reduced efficiency of nonsense-mediated decay. The results emphasize that mRNA analysis is important in defining Becker mutations and will be of value in assessing various gene therapy strategies.

Although

    Becker muscular dystrophy (BMD
    DIAGNOSIS

; MIM 300376) is mainly caused by

    gross deletions of the dystrophin gene
    GENETICS

, the nature of the mutations involved in the remaining cases is of importance because of the milder clinical course of

    Becker
    DIAGNOSIS

. We have extensively characterized the

    mRNA changes
    GENETICS

 associated with five

    novel point mutations
    GENETICS

 giving rise to a

    Becker
    DIAGNOSIS

 phenotype, which confirm that

    Becker
    DIAGNOSIS

 arises largely due to

    alterations in splicing
    GENETICS

. In two cases the milder phenotype arises because of

    exon skipping, leading to an in-frame deletion (c.1603-2A>C and c.4250T>A)
    GENETICS

. In further two cases

    intronic mutations (c.4519-5C>G and c.961-5925A>C)
    GENETICS

 result in

    complex splicing changes
    GENETICS

, but with some residual normal transcripts. The last case,

    c.10412T>A (p.Leu3471X), results in a truncated transcript missing only part of the COOH terminal of the protein
    GENETICS

, suggesting that

    this region is not crucial for dystrophin function
    GENETICS

. The

    detection of a low amount of dystrophin
    BIOCHEMICAL

 in this patient could be attributable to a

    reduced efficiency of nonsense-mediated decay
    BIOCHEMICAL

. The results emphasize that

    mRNA analysis
    PARACLINICAL

 is important in defining

    Becker
    DIAGNOSIS

 mutations and will be of value in assessing various gene therapy strategies.

Becker muscular dystrophy (BMD
Becker
Becker
Becker
Becker


Anesthesia for Duchenne muscular dystrophy patients: case reports.

Reporting two cases of anesthesia in Duchenne Muscular Dystrophy (DMD) patients, which is an uncommon, progressive and disabling disease, and discussing anesthetic approaches, impairment of pulmonary and cardiac functions, the possibility of malignant hyperthermia, increased sensitivity to neuromuscular blockers and increased postoperative morbidity are some challenges faced by anesthesiologists.

First case was a pediatric patient with DMD and rhabdomyosarcoma, scheduled for tumor excision and cervical emptying. During preanesthetic evaluation, history, clinical and additional exams, no changes were detected except for the cervical tumor. We decided for total intravenous anesthesia with remifentanil administered by continuous infusion and propofol by target-controlled infusion without neuromuscular blockers. Surgery lasted 180 minutes without intercurrences. The second case was a male patient, 24 years old, with DMD and cholelithiasis with surgical indication who, during preoperative evaluation, has revealed severe restrictive pneumopathy with decreased capacity and respiratory reserves and the need for nasal BIPAP at night. For this patient we decided for tracheal intubation with minimum sedation and topic anesthesia, followed by total intravenous anesthesia with remifentanil administered by continuous infusion and propofol by target-controlled infusion without neuromuscular blockers. At the end, patient was extubated still in to operating room and nasal BIPAP was immediately placed, being patient referred to the ICU. Patient was discharged from ICU in the 2nd PO day and from hospital in the 3rd PO day.

Total intravenous anesthesia with propofol and remifentanil administered by continuous infusion without neuromuscular blockers is a safe and effective option for DMD patients.

Reporting two cases of

    anesthesia
    MEDICATION

 in

    Duchenne Muscular Dystrophy (DMD)
    DIAGNOSIS

 patients, which is an uncommon, progressive and disabling disease, and discussing

    anesthetic approaches
    MEDICATION

,

    impairment of pulmonary and cardiac functions
    SYMPTOMS

, the possibility of

    malignant hyperthermia
    SYMPTOMS

,

    increased sensitivity to neuromuscular blockers
    SYMPTOMS

 and

    increased postoperative morbidity
    SYMPTOMS

 are some challenges faced by

    anesthesiologists
    PARACLINICAL

.

First case was a

    pediatric
    AGE

 patient with

    DMD
    DIAGNOSIS

 and

    rhabdomyosarcoma
    DIAGNOSIS

, scheduled for

    tumor excision
    MEDICATION

 and

    cervical emptying
    MEDICATION

. During preanesthetic evaluation,

    history, clinical and additional exams
    PARACLINICAL

,

    no changes were detected
    NEG_FINDINGS

 except for the

    cervical tumor
    SYMPTOMS

. We decided for

    total intravenous anesthesia with remifentanil administered by continuous infusion and propofol by target-controlled infusion without neuromuscular blockers
    MEDICATION

.

    Surgery lasted 180 minutes
    MEDICATION

    without intercurrences
    NEG_FINDINGS

. The second case was a

    male
    GENDER

 patient,

    24 years old
    AGE

, with

    DMD
    DIAGNOSIS

 and

    cholelithiasis
    DIAGNOSIS

 with

    surgical indication
    MEDICATION

 who, during preoperative evaluation, has revealed

    severe restrictive pneumopathy
    SYMPTOMS

 with

    decreased capacity and respiratory reserves
    SYMPTOMS

 and the

    need for nasal BIPAP
    MEDICATION

 at night. For this patient we decided for

    tracheal intubation with minimum sedation and topic anesthesia
    MEDICATION

, followed by

    total intravenous anesthesia with remifentanil administered by continuous infusion and propofol by target-controlled infusion without neuromuscular blockers
    MEDICATION

. At the end, patient was

    extubated still in to operating room
    MEDICATION

 and

    nasal BIPAP was immediately placed
    MEDICATION

, being patient

    referred to the ICU
    MEDICATION

. Patient was

    discharged from ICU
    MEDICATION

 in the 2nd PO day and from hospital in the 3rd PO day.

    Total intravenous anesthesia with propofol and remifentanil administered by continuous infusion without neuromuscular blockers
    MEDICATION

 is a safe and effective option for

    DMD
    DIAGNOSIS

 patients.

Duchenne Muscular Dystrophy (DMD)
DMD
rhabdomyosarcoma
DMD
cholelithiasis
DMD

no changes were detected
without intercurrences


Novel mutation (Gly280Ala) in the ATP-binding domain of glycerol kinase causes severe hyperglycerolemia.

Glycerol kinase deficiency is a rarely diagnosed X-linked recessive disorder which occurs as a complex form together with the adrenal hypoplasia congenita (AHC) or with Duchenne muscular dystrophy (DMD) or as an isolated form either symptomatic or asymptomatic. We report the case of a male adult who had pseudo-hypertriglyceridemia (falsely elevated triglycerides of 552 mg/dl) refractory to lipid-lowering therapy for more than 15 years. Further investigations revealed an isolated, asymptomatic glycerol kinase deficiency. Using polymerase chain reaction and direct DNA sequencing, a novel missense mutation Gly280Ala in the Xp21.3 glycerol kinase gene was found. Comparison between human and E.coli glycerol kinase showed that the mutation affects a highly conserved amino acid in an ATP-binding domain in the active centre. This mutation is assumed to destabilize a hydrogen bond between ligand and enzyme resulting in a reduced activity of glycerol kinase and therefore in hyperglycerolemia.

    Glycerol kinase deficiency
    BIOCHEMICAL

 is a rarely diagnosed

    X-linked recessive disorder
    GENETICS

 which occurs as a complex form together with the

    adrenal hypoplasia congenita (AHC)
    DIAGNOSIS

 or with

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 or as an isolated form either symptomatic or

    asymptomatic
    NEG_FINDINGS

. We report the case of a

    male
    GENDER

    adult
    AGE

 who had

    pseudo-hypertriglyceridemia
    BIOCHEMICAL

 (

    falsely elevated triglycerides of 552 mg/dl)
    BIOCHEMICAL

    refractory to lipid-lowering therapy for more than 15 years
    NEG_FINDINGS

. Further investigations revealed an

    isolated, asymptomatic glycerol kinase deficiency
    BIOCHEMICAL

. Using

    polymerase chain reaction and direct DNA sequencing
    PARACLINICAL

, a

    novel missense mutation Gly280Ala in the Xp21.3 glycerol kinase gene
    GENETICS

 was found.

    Comparison between human and E.coli glycerol kinase
    PARACLINICAL

 showed that the

    mutation affects a highly conserved amino acid in an ATP-binding domain in the active centre
    GENETICS

. This mutation is assumed to

    destabilize a hydrogen bond between ligand and enzyme
    BIOCHEMICAL

 resulting in a

    reduced activity of glycerol kinase
    BIOCHEMICAL

 and therefore in

    hyperglycerolemia
    BIOCHEMICAL

.

adrenal hypoplasia congenita (AHC)
Duchenne muscular dystrophy (DMD)


Tracheoinnominate fistula in a Duchenne muscular dystrophy patient: successful management with an endovascular stent.

Tracheoinnominate fistula is a rare but often fatal complication occurring in Duchenne Muscular Dystrophy (DMD) patients with long-term tracheostomy. We report a 16-year-old boy with DMD who developed a fistula causing massive haemorrhage 26 months after tracheostomy. Due to the high risk of perioperative complications, a minimally invasive technique with placement of an endovascular stent grafting the innominate artery was performed. The patient was successfully managed and recovered uneventfully. We believe that endovascular repair of tracheoinnominate fistula by stent grafting may be the treatment of choice in severely compromised patients and that clinicians who treat tracheostomised DMD patients should be familiar with this management strategy.

    Tracheoinnominate fistula
    SYMPTOMS

 is a rare but often fatal complication occurring in

    Duchenne Muscular Dystrophy (DMD)
    DIAGNOSIS

 patients with

    long-term tracheostomy
    MEDICATION

. We report a

    16-year-old
    AGE

    boy
    GENDER

 with

    DMD
    DIAGNOSIS

 who developed a

    fistula causing massive haemorrhage
    SYMPTOMS

 26 months after

    tracheostomy
    MEDICATION

. Due to the high risk of

    perioperative complications
    SYMPTOMS

, a

    minimally invasive technique with placement of an endovascular stent grafting the innominate artery
    MEDICATION

 was performed. The patient was successfully managed and recovered uneventfully. We believe that

    endovascular repair of tracheoinnominate fistula
    MEDICATION

    by stent grafting
    MEDICATION

 may be the treatment of choice in severely compromised patients and that clinicians who treat

    tracheostomised
    MEDICATION

    DMD
    DIAGNOSIS

 patients should be familiar with this management strategy.

Tracheoinnominate fistula
fistula causing massive haemorrhage
perioperative complications

Duchenne Muscular Dystrophy (DMD)
DMD
DMD


Midwall myocardial fibrosis in Becker-Kiener muscular dystrophy.

We report on a 38- year-old man with Becker-Kiener muscular dystrophy (BMD) and dilated cardiomyopathy without clinical symptoms of congestive heart failure who was referred for risk evaluation of sudden cardiac death. The degree of cardiac involvement in BMD varies greatly from no or hardly any cardiac abnormality to severe arrhythmias, dilatative cardiomyopathy and heart failure to heart transplantation or sudden cardiac death. These cardiac abnormalities have been related to replacement of the cardiomyocytes by connecting tissue or fat. In the clinical setting, cardiovascular magnetic resonance (CMR) has been proved to be a valid non-invasive method for obtaining anatomical and structural information of the heart. Furthermore, gadolinium-enhanced CMR can also characterize areas of myocardial fibrosis. Demonstration of extensive areas of fibrosis in an early stage of the disease might be a surrogate marker for an impaired clinical outcome. Therefore, serial CMR examinations starting upon diagnosis of the disease should be considered, as this may lead to an earlier recognition of cardiac involvement and may affect further management of the patient.

We report on a

    38- year-old
    AGE

    man
    GENDER

 with

    Becker-Kiener muscular dystrophy (BMD)
    DIAGNOSIS

 and

    dilated cardiomyopathy
    DIAGNOSIS

    without clinical symptoms of congestive heart failure
    NEG_FINDINGS

 who was referred for risk evaluation of

    sudden cardiac death
    SYMPTOMS

. The degree of

    cardiac involvement
    SYMPTOMS

 in

    BMD
    DIAGNOSIS

 varies greatly from

    no or hardly any cardiac abnormality
    NEG_FINDINGS

 to

    severe arrhythmias
    SYMPTOMS

,

    dilatative cardiomyopathy
    SYMPTOMS

 and

    heart failure
    SYMPTOMS

 to

    heart transplantation
    MEDICATION

 or

    sudden cardiac death
    SYMPTOMS

. These

    cardiac abnormalities
    SYMPTOMS

 have been related to

    replacement of the cardiomyocytes by connecting tissue or fat
    MICROSCOPIC

. In the clinical setting,

    cardiovascular magnetic resonance (CMR)
    PARACLINICAL

 has been proved to be a valid

    non-invasive
    PARACLINICAL

 method for obtaining

    anatomical and structural information of the heart
    PARACLINICAL

. Furthermore,

    gadolinium-enhanced CMR
    PARACLINICAL

 can also characterize

    areas of myocardial fibrosis
    SYMPTOMS

. Demonstration of

    extensive areas of fibrosis
    SYMPTOMS

 in an early stage of the disease might be a surrogate marker for an impaired clinical outcome. Therefore,

    serial CMR examinations
    PARACLINICAL

 starting upon diagnosis of the disease should be considered, as this may lead to an earlier recognition of

    cardiac involvement
    SYMPTOMS

 and may affect further management of the patient.

Becker-Kiener muscular dystrophy (BMD)
dilated cardiomyopathy
BMD

sudden cardiac death
cardiac involvement
severe arrhythmias
dilatative cardiomyopathy
heart failure
sudden cardiac death
cardiac abnormalities
areas of myocardial fibrosis
extensive areas of fibrosis
cardiac involvement


[Surgical treatment of acquired myogenic eyelid ptosis].

To report the surgical outcome of aponeurosis surgery in patients with acquired myogenic eyelid ptosis and describe surgical guidelines for their correction.

The clinical records of two patients with acquired myogenic eyelid ptosis after surgical correction were reviewed.

In two patients with acquired myogenic eyelid ptosis and barely good levator function, levator resection surgery was performed. Corneal complications appeared in both cases.

Patients with acquired myogenic eyelid ptosis are at risk of post-operative surgical complications from corneal exposure. Surgical correction should be conservative and performed only when the visual axis is compromised.

To report the surgical outcome of

    aponeurosis surgery
    MEDICATION

 in patients with

    acquired myogenic eyelid ptosis
    SYMPTOMS

 and describe surgical guidelines for their correction.

The clinical records of two patients with

    acquired myogenic eyelid ptosis
    SYMPTOMS

 after

    surgical correction
    MEDICATION

 were reviewed.

In two patients with

    acquired myogenic eyelid ptosis
    SYMPTOMS

 and

    barely good levator function
    NEG_FINDINGS

,

    levator resection surgery
    MEDICATION

 was performed.

    Corneal complications
    SYMPTOMS

 appeared in both cases.

Patients with

    acquired myogenic eyelid ptosis
    SYMPTOMS

 are at risk of

    post-operative surgical complications from corneal exposure
    SYMPTOMS

.

    Surgical correction
    MEDICATION

 should be

    conservative
    MEDICATION

 and performed only when the visual axis is compromised.

aponeurosis surgery
surgical correction
levator resection surgery
Surgical correction
conservative


A G-to-A transition at the fifth position of intron-32 of the dystrophin gene inactivates a splice-donor site both in vivo and in vitro.

The splicing pattern of pre-mRNA is unpredictable in genes harboring a single-nucleotide change within the consensus sequence of a splice-donor site. In the dystrophin gene, a transition from G to A at the fifth position of intron-32 (4518+5G > A) has been reported as a polymorphism within the consensus sequence or a mutation identified in Duchenne muscular dystrophy (DMD). Here, we report both in vivo and in vitro evidence that shows inactivation of the splice-donor site caused by this mutation. In one Japanese DMD case, two novel dystrophin mRNAs were identified in the patient's lymphocytes, one with a 98 bp deletion of the 3' end of exon-32 (dys32-98) and the other with a 28 bp intron retained between exons 32 and 33 (dys32 + 28). Genomic sequencing disclosed a single-nucleotide change from G to A at the fifth position of intron-32 (4518+5G > A). To demonstrate in vitro the inactivation of this splice-donor site by this nucleotide change, mini-dystrophin genes comprising three exons harboring either normal or mutant intron-32 sequences were expressed in HeLa cells, and the splicing products were analyzed by reverse-transcription PCR amplification. A normal transcript consisting of three exons was obtained from the normal construct. From the mutant, we obtained one product containing a 98 bp deletion at the 3' end of exon-32, indicating complete inactivation of the native splice-donor site. Thus, both in vivo and in vitro experiments demonstrate that 4518+5G > A causes a splicing error leading to transcript termination; it did not behave like a silent polymorphism. Our results indicate that the in vitro splicing system is a powerful tool for determining the underlying mechanism of a disease-causing mutation in a splicing consensus sequence.

The splicing pattern of pre-mRNA is unpredictable in genes harboring a

    single-nucleotide change within the consensus sequence of a splice-donor site
    GENETICS

. In the

    dystrophin gene
    GENETICS

, a

    transition from G to A at the fifth position of intron-32 (4518+5G > A)
    GENETICS

 has been reported as a

    polymorphism within the consensus sequence
    GENETICS

 or a mutation identified in

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

. Here, we report both in vivo and in vitro evidence that shows

    inactivation of the splice-
    GENETICS

donor site caused by this mutation. In one

    Japanese
    ETHNICITY

    DMD
    DIAGNOSIS

 case, two

    novel dystrophin mRNAs
    GENETICS

 were identified in the patient's lymphocytes, one

    with a 98 bp deletion of the 3' end of exon-32 (dys32-98) and the other with a 28 bp intron retained between exons 32 and 33 (dys32 + 28)
    GENETICS

.

    Genomic sequencing
    PARACLINICAL

 disclosed a

    single-nucleotide change from G to A at the fifth position of intron-32 (4518+5G > A)
    GENETICS

. To demonstrate in vitro the

    inactivation of this splice-donor site by this nucleotide change
    GENETICS

, mini-dystrophin genes comprising three exons harboring either

    normal or mutant intron-32 sequences
    GENETICS

 were expressed in HeLa cells, and the splicing products were analyzed by

    reverse-transcription PCR amplification
    PARACLINICAL

. A

    normal transcript consisting of three exons
    GENETICS

 was obtained from the normal construct. From the mutant, we obtained one product

    containing a 98 bp deletion at the 3' end of exon-32, indicating complete inactivation of the native splice-donor site
    GENETICS

. Thus, both in vivo and in vitro experiments demonstrate that

    4518+5G > A causes a splicing error leading to transcript termination
    GENETICS

; it did not behave like a

    silent polymorphism
    GENETICS

. Our results indicate that the

    in vitro splicing system
    PARACLINICAL

 is a powerful tool for determining the underlying mechanism of a disease-causing mutation in a splicing consensus sequence.


The interface of genomic technologies and nursing.

(a) to summarize views of the interface of technology, genomic technology, and nursing; (b) provide an overview of current and emerging genomic technologies; (c) present clinical exemplars of uses of genomic technology in two disease conditions; and (d) list genomic-focused nursing research on genomic technologies.

A discussion of genomic technology in the context of nurses' views of technology, the importance of genomic technology for nurses, linking the central dogma of molecular biology to state-of-the-art tests and assays, and nurses' current use of technologies.

Human genome discoveries will continue to be an integral part of disease prevention, diagnosis, treatment, and management. These discoveries also have the potential for being integrated into nursing science. Genomic technologies are becoming a driving force in patient management, so that nurses will be unable to provide quality care without knowledge of the types of genomic technologies, the rationale for their use, and the possible sequelae that can result from genetic diagnosis or treatment. Many nurses already are using genomic technologies to conduct genomic-focused nursing research. The biobehavioral nature of much of this research further indicates the important contributions of nurses in genomics.

(a) to summarize views of the interface of technology,

    genomic technology
    MEDICATION

, and nursing; (b) provide an overview of current and emerging genomic technologies; (c) present clinical exemplars of uses of

    genomic technology
    MEDICATION

 in two disease conditions; and (d) list genomic-focused nursing research on

    genomic technologies
    MEDICATION

.

Human genome discoveries will continue to be an integral part of disease prevention, diagnosis, treatment, and management. These discoveries also have the potential for being integrated into nursing science. Genomic technologies are becoming a driving force in patient management, so that nurses will be unable to provide quality care without knowledge of the types of genomic technologies, the rationale for their use, and the possible sequelae that can result from genetic diagnosis or treatment. Many nurses already are using

    genomic technologies
    MEDICATION

 to conduct genomic-focused nursing research. The biobehavioral nature of much of this research further indicates the important contributions of nurses in genomics.

genomic technology
genomic technology
genomic technologies
genomic technologies


[Allogeneic umbilical cord blood stem cell transplantation in Duchenne muscular dystrophy].

To study the feasibility of treatment of Duchenne muscular dystrophy (DMD) with umbilical cord stem cell transplantation.

HLA matching was conducted for a 11-year-old DMD boy with family history was underwent umbilical cord blood stem cell transplantation and a sample of umbilical cord stem cells with 5 matched HLA sites was found in the cord blood bank with 27.32 x 10(8) nucleated cells, about 2.6 times that of the treatment dosage for him. After pretreatment with busulfan 14 mg/kg.d, cyclophosphamide 50 mg/kg.d, and rabbit anti-human thymocyte globulin 10 mg/kg.d, the allogeneic cord blood stem cells were transplanted intravenously. Cyclosporin A, methylprednisolone and MMF were used after the transplantation so as to prevent graft versus host reaction. Prostaglandin E1 was used to prevent Budd-Chiari syndrome, and ganciclovir was used to prevent cytomegalovirus infection. At the same time, Gran, granulocytic cell stimulating factor, and gammaglobulin were also used. Biochemistry test, including serum creatine kinase (CK), was conducted. Evidence of reconstruction of blood making, including conversion of blood type, was observed. PCR-STR analysis was used to observe the status of implantation of the donor umbilical cord blood stem cells.

(1) 12 days after transplantation, the white blood cells (WBC) of peripheral blood were 0.5 x 10(9)/L, 14 days after, the numbers of WBC and neutrophils were 1.0 x 10(9)/L and 0.6 x 10(9)/L respectively. In 37 days, granulocytic cell stimulating factor was no more used, the peripheral blood WBC fluctuated around 3.34 approximately 12.2 x 10(9)/L. In the 27th day, the number of blood platelets was more than 20 x 10(9)/L and hemoglobin rose to 88 g/L. On the 24th day red blood cells transfusion was stopped. (2) In the 42nd day, the blood type of the patient transformed from type A before transplantation to type AB (the blood type of transplanted stem cells is type B). (3) PCR-STR test of the peripheral blood made 17, 26, and 42 days after transplantation showed that the gene type of the patient was mixed mosaic: The ratio of donor gradually increased from 40% approximately 45% to 55% approximately 65%. (4) In the 38th day I degrees GVHD appeared. (5) serum CK level declined from 6000 U/L to 600 approximately 2200 U/L. (6) In the 42nd day, physical examination revealed obviously improvement in walking, turning the body over, and standing up.

This is first case of prospective clinical transplantation on DMD by allogeneic cord blood stem cell. Umbilical cord stem cell transplantation helps re-build blood-making function, and improve locomotive function with a mild GVHD reaction. The genotype of rebuilt blood is mosaic but the ratio of gene mosaic gradually turn from recipient gene type > donor gene type to recipient gene type < donor gene type. The serum CK level decreases significantly after transplantation, which may slow down the necrosis of muscle cell. DMD patient will be benefited by stem cell transplantation.

To study the feasibility of treatment of

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

    with umbilical cord stem cell transplantation
    MEDICATION

.

    HLA matching
    PARACLINICAL

 was conducted for a

    11-year-old
    AGE

    DMD
    AGE

    boy
    GENDER

 with

    family history
    FAMILY

 was underwent

    umbilical cord blood stem cell transplantation
    MEDICATION

 and a

    sample of umbilical cord stem cells with 5 matched HLA sites was found in the cord blood bank with 27.32 x 10(8) nucleated cells, about 2.6 times that of the treatment dosage
    MEDICATION

 for him. After

    pretreatment with busulfan 14 mg/kg.d, cyclophosphamide 50 mg/kg.d, and rabbit anti-human thymocyte globulin 10 mg/kg.d, the allogeneic cord blood stem cells were transplanted intravenously
    MEDICATION

.

    Cyclosporin A, methylprednisolone and MMF were used after the transplantation
    MEDICATION

 so as to prevent

    graft versus host reaction
    SYMPTOMS

.

    Prostaglandin E1
    MEDICATION

 was used to prevent

    Budd-Chiari syndrome
    DIAGNOSIS

, and

    ganciclovir
    MEDICATION

 was used to prevent

    cytomegalovirus infection
    DIAGNOSIS

. At the same time,

    Gran, granulocytic cell stimulating factor, and gammaglobulin
    MEDICATION

 were also used.

    Biochemistry test, including serum creatine kinase (CK)
    PARACLINICAL

, was conducted.

    Evidence of reconstruction of blood making, including conversion of blood type
    MICROSCOPIC

, was observed.

    PCR-STR analysis
    PARACLINICAL

 was used to observe the status of implantation of the

    donor umbilical cord blood stem cells
    MEDICATION

.

(1) 12 days after

    transplantation
    MEDICATION

,

    the white blood cells (WBC) of peripheral blood were 0.5 x 10(9)/L
    BIOCHEMICAL

, 14 days after,

    the numbers of WBC and neutrophils were 1.0 x 10(9)/L and 0.6 x 10(9)/L respectively
    BIOCHEMICAL

. In 37 days,

    granulocytic cell stimulating factor was no more used
    MEDICATION

, the peripheral blood WBC fluctuated around 3.34 approximately 12.2 x 10(9)/L. In the 27th day, the

    number of blood platelets was more than 20 x 10(9)/L
    BIOCHEMICAL

 and hemoglobin rose to 88 g/L. On the 24th day

    red blood cells transfusion was stopped
    MEDICATION

. (2) In the 42nd day, the blood type of the patient

    transformed from type A
    MICROSCOPIC

 before

    transplantation
    MEDICATION

    to type AB
    MICROSCOPIC

 (the

    blood type of transplanted stem cells is type B)
    MICROSCOPIC

. (3)

    PCR-STR test of the peripheral blood made
    PARACLINICAL

 17, 26, and 42 days after

    transplantation
    MEDICATION

 showed that the

    gene type of the patient was mixed mosaic
    GENETICS

: The

    ratio of donor gradually increased from 40% approximately 45% to 55% approximately 65%
    GENETICS

. (4) In the 38th day

    I degrees GVHD appeared
    SYMPTOMS

. (5) serum CK level declined from 6000 U/L to 600 approximately 2200 U/L. (6) In the 42nd day, physical examination revealed

    obviously improvement in walking, turning the body over, and standing up
    SYMPTOMS

.

This is first case of

    prospective clinical transplantation
    MEDICATION

 on

    DMD
    DIAGNOSIS

 by

    allogeneic cord blood stem cell
    MEDICATION

.

    Umbilical cord stem cell transplantation
    MEDICATION

 helps

    re-build blood-making function
    SYMPTOMS

, and

    improve locomotive function
    SYMPTOMS

 with a

    mild GVHD reaction
    SYMPTOMS

. The

    genotype of rebuilt blood is mosaic but the ratio of gene mosaic gradually turn from recipient gene type > donor gene type to recipient gene type < donor gene type
    GENETICS

. The

    serum CK level decreases significantly
    BIOCHEMICAL

 after

    transplantation
    MEDICATION

, which may slow down the

    necrosis of muscle cell
    MICROSCOPIC

.

    DMD
    DIAGNOSIS

 patient will be benefited by

    stem cell transplantation
    MEDICATION

.

Duchenne muscular dystrophy (DMD)
Budd-Chiari syndrome
cytomegalovirus infection
DMD
DMD


Beta-sarcoglycanopathy (LGMD 2E) in a Spanish family.

Out of 10 autosomal recessive limb-girdle muscular dystrophies reported, 4 are caused by mutations in the genes encoding for sarcoglycans (alpha-, beta-, gamma- and delta-SG). Beta-sarcoglycanopathy (limb-girdle muscular dystrophy 2E) is a genetically heterogeneous disorder which usually presents a severe progressive clinical course. A complete immunohistochemical evaluation of the sarcoglycan complex should be carried out to direct the mutation analysis approach. The present report concerns a Spanish family with a genetically confirmed beta-sarcoglycanopathy. The patient, a 16-year-old female, offspring of a consanguineous marriage, developed a severe limb-girdle muscular dystrophy with a Duchenne-like phenotype. Muscle biopsy showed dystrophic changes and complete absence of the four sarcoglycans. Genetic analysis demonstrated homozygosis for the M100K missense mutation in exon 3, encoding for the proximal extracellular domain. The parents and one sister were found to be carriers. Missense mutations affecting this domain result in the instability of the entire sarcoglycan complex and lead to severe phenotypes as seen in non-sense mutations.

Out of 10

    autosomal recessive
    GENETICS

    limb-girdle muscular dystrophies
    DIAGNOSIS

 reported, 4 are caused by

    mutations in the genes encoding for sarcoglycans (alpha-, beta-, gamma- and delta-SG)
    GENETICS

.

    Beta-sarcoglycanopathy (limb-girdle muscular dystrophy 2E)
    DIAGNOSIS

 is a

    genetically heterogeneous disorder
    GENETICS

 which usually presents a

    severe progressive clinical course
    SYMPTOMS

. A complete

    immunohistochemical evaluation of the sarcoglycan complex
    PARACLINICAL

 should be carried out to direct the mutation analysis approach. The present report concerns a

    Spanish
    ETHNICITY

    family with a
    FAMILY

 genetically confirmed

    beta-sarcoglycanopathy
    DIAGNOSIS

. The patient, a

    16-year-old
    AGE

    female
    GENDER

,

    offspring of a consanguineous marriage
    FAMILY

, developed a

    severe limb-girdle muscular dystrophy
    DIAGNOSIS

    with a Duchenne-like phenotype
    SYMPTOMS

.

    Muscle biopsy
    PARACLINICAL

 showed

    dystrophic changes
    SYMPTOMS

 and

    complete absence of the four sarcoglycans
    MICROSCOPIC

.

    Genetic analysis
    PARACLINICAL

 demonstrated

    homozygosis for the M100K missense mutation in exon 3, encoding for the proximal extracellular domain
    GENETICS

.

    The parents and one sister were found to be carriers
    FAMILY

.

    Missense mutations affecting this domain
    GENETICS

 result in the

    instability of the entire sarcoglycan complex
    MICROSCOPIC

 and lead to severe phenotypes as seen in

    non-sense mutations
    GENETICS

.

severe progressive clinical course
with a Duchenne-like phenotype
dystrophic changes


Rapid progression from hypertrophic cardiomyopathy to heart failure in a patient with Becker's muscular dystrophy.

We describe the case of a 17-year-old boy with Becker's muscular dystrophy (BMD) presenting with rapid progression from hypertrophic cardiomyopathy to heart failure within 2 years. Initial echocardiogram showed severe hypertrophy of left ventricle (LV) and right ventricle (RV) with normal chamber size, and preserved LV systolic function. Microscopic study of cardiac muscle obtained by endomyocardial biopsy of the interventricular septum showed severe hypertrophy of the muscle fibers and interstitial fibrosis. Follow-up echocardiogram 2 years after the first examination exhibited marked dilated LV and RV with severe LV global hypokinesia. Follow-up endomyocardial biopsy demonstrated increased interstitial cellular matrix. Immunohistochemical staining for dystrophin revealed significant loss of dystrophin along the sarcoplasmic membrane of the right biceps brachii muscle, compatible with BMD.

We describe the case of a

    17-year-old
    AGE

    boy
    GENDER

 with

    Becker's muscular dystrophy (BMD)
    DIAGNOSIS

 presenting with

    rapid progression from hypertrophic cardiomyopathy
    SYMPTOMS

 to

    heart failure
    SYMPTOMS

 within 2 years.

    Initial echocardiogram
    PARACLINICAL

 showed

    severe hypertrophy of left ventricle (LV) and right ventricle (RV)
    SYMPTOMS

 with

    normal chamber size
    NEG_FINDINGS

, and

    preserved LV systolic function
    NEG_FINDINGS

.

    Microscopic study of cardiac muscle obtained by endomyocardial biopsy of the interventricular septum
    PARACLINICAL

 showed

    severe hypertrophy of the muscle fibers
    MICROSCOPIC

 and

    interstitial fibrosis
    MICROSCOPIC

.

    Follow-up echocardiogram 2 years
    PARACLINICAL

 after the first examination exhibited

    marked dilated LV and RV
    SYMPTOMS

 with

    severe LV global hypokinesia
    SYMPTOMS

.

    Follow-up endomyocardial biopsy
    PARACLINICAL

 demonstrated

    increased interstitial cellular matrix
    MICROSCOPIC

.

    Immunohistochemical staining for dystrophin
    PARACLINICAL

 revealed

    significant loss of dystrophin along the sarcoplasmic membrane of the right biceps brachii muscle
    MICROSCOPIC

, compatible with

    BMD
    DIAGNOSIS

.

normal chamber size
preserved LV systolic function


Worsening of heart failure in Becker muscular dystrophy after nonsteroidal anti-inflammatory drugs.

A 40-year-old male with Becker muscular dystrophy and cardiac involvement was stable in New York Heart Association class II for 7 years. He then had arthralgia caused by bilateral gonarthrosis. He received diclofenac 100 mg/d and 500 mg/d mephenamine acid. Six weeks later, he was hospitalized because of heart failure (New York Heart Association class IV). Echocardiography revealed biatrial and biventricular dilation, a left ventricular end-diastolic diameter of 82 mm, an ejection fraction of 26%, a severe tricuspid regurgitation, and an elevated pulmonary artery pressure of 60 mm Hg. Nonsteroidal anti-inflammatory drugs were discontinued, and physiotherapy and equipment with a corset were initiated. He improved after treatment with parenteral diuretics, returning to class II. Nonsteroidal anti-inflammatory drugs should be given with caution in Becker muscular dystrophy with cardiac involvement.

A

    40-year-old
    AGE

    male
    GENDER

 with

    Becker muscular dystrophy
    DIAGNOSIS

 and

    cardiac involvement
    SYMPTOMS

 was

    stable in New York Heart Association class II for 7 years
    SYMPTOMS

.

    He
    GENDER

 then had

    arthralgia
    SYMPTOMS

 caused by

    bilateral gonarthrosis
    SYMPTOMS

. He

    received diclofenac 100 mg/d and 500 mg/d mephenamine acid
    MEDICATION

. Six weeks later,

    he
    GENDER

 was hospitalized because of

    heart failure (New York Heart Association class IV)
    SYMPTOMS

.

    Echocardiography
    PARACLINICAL

 revealed

    biatrial and biventricular dilation
    SYMPTOMS

, a

    left ventricular end-diastolic diameter of 82 mm
    SYMPTOMS

, an

    ejection fraction of 26%
    SYMPTOMS

, a

    severe tricuspid regurgitation
    SYMPTOMS

, and an

    elevated pulmonary artery pressure of 60 mm Hg
    SYMPTOMS

.

    Nonsteroidal anti-inflammatory drugs were discontinued
    NEG_FINDINGS

, and

    physiotherapy and equipment with a corset
    MEDICATION

 were initiated. He improved after

    treatment with parenteral diuretics
    MEDICATION

,

    returning to class II
    SYMPTOMS

.

    Nonsteroidal anti-inflammatory drugs
    MEDICATION

 should be given with caution in

    Becker muscular dystrophy
    DIAGNOSIS

 with

    cardiac involvement
    SYMPTOMS

.

Becker muscular dystrophy
Becker muscular dystrophy


Identification of novel mutations of the DAX-1 gene in patients with X-linked adrenal hypoplasia congenita.

X-linked adrenal hypoplasia congenita (AHC) is a condition clinically featuring adrenal insufficiency and hypogonadotropic hypogonadism caused by mutations of DAX-1. This study was undertaken to characterize the molecular defects of DAX-1 in 3 unrelated Korean patients with AHC.

Patient 1 is a 6-year-old boy who presented with a salt-losing adrenal crisis in the neonatal period. Patient 2 is a 3-year-old boy who manifested aspiration pneumonia and adrenal insufficiency at the age of 1 month. Patient 3 is a 7-year-old boy who developed an adrenal crisis at the age of 3 days. In each of these patients, DAX-1 was analyzed by direct DNA sequencing after polymerase chain reaction amplification of the entire coding region.

Direct sequencing of DAX-1 revealed two novel mutations, 1156_1157delCT in patient 1 and another novel nonsense mutation W105X in patient 2. Patient 3 had complete deletion of DAX-1. In patient 3, serum transaminases and creatine kinase levels were elevated while the glycerol kinase activity of leukocytes was decreased. Markedly elevated glycerol excretion was detected by urine organic acid analysis. Patient 3 was diagnosed as Xp21 contiguous gene syndrome associated with deletions of the entire IL1RAPL, GK genes and the C-terminal region of DMD gene.

Two novel mutations of DAX-1 were detected in 2 unrelated patients with AHC, and complete deletion of DAX-1 in a patient with Xp21 contiguous gene syndrome who also presented with glycerol kinase deficiency, Duchenne muscular dystrophy, and AHC.

    X-linked adrenal hypoplasia congenita (AHC)
    GENETICS

 is a condition clinically featuring

    adrenal insufficiency
    SYMPTOMS

 and

    hypogonadotropic hypogonadism
    SYMPTOMS

 caused by

    mutations of DAX-1
    GENETICS

. This study was undertaken to characterize the

    molecular defects of DAX-1
    GENETICS

 in 3 unrelated

    Korean
    ETHNICITY

 patients with

    AHC
    DIAGNOSIS

.

Patient 1 is a

    6-year-old
    AGE

    boy
    GENDER

 who presented with a

    salt-losing adrenal crisis
    SYMPTOMS

 in the

    neonatal period
    AGE

. Patient 2 is a

    3-year-old
    AGE

    boy
    GENDER

 who manifested

    aspiration pneumonia
    DIAGNOSIS

 and

    adrenal insufficiency
    SYMPTOMS

 at the

    age of 1 month
    AGE

. Patient 3 is a

    7-year-old
    AGE

    boy
    GENDER

 who developed an

    adrenal crisis
    SYMPTOMS

 at the

    age of 3 days
    AGE

. In each of these patients,

    DAX-1
    PARACLINICAL

 was analyzed by

    direct DNA sequencing after polymerase chain reaction amplification of the entire coding region
    PARACLINICAL

.

    Direct sequencing of DAX-1
    PARACLINICAL

 revealed

    two novel mutations, 1156_1157delCT
    GENETICS

 in patient 1 and another

    novel nonsense mutation W105X
    GENETICS

 in patient 2. Patient 3 had

    complete deletion of DAX-1
    GENETICS

. In patient 3,

    serum transaminases and creatine kinase levels were elevated
    BIOCHEMICAL

 while

    the glycerol kinase activity of leukocytes was decreased
    BIOCHEMICAL

.

    Markedly elevated glycerol excretion was detected
    BIOCHEMICAL

 by

    urine organic acid analysis
    BIOCHEMICAL

. Patient 3 was diagnosed as

    Xp21 contiguous gene syndrome
    DIAGNOSIS

 associated with

    deletions of the entire IL1RAPL, GK genes and the C-terminal region of DMD gene
    GENETICS

.

    Two novel mutations of DAX-1
    GENETICS

 were detected in 2 unrelated patients with

    AHC
    DIAGNOSIS

, and

    complete deletion of DAX-1
    GENETICS

 in a patient with

    Xp21 contiguous gene syndrome
    DIAGNOSIS

 who also presented with

    glycerol kinase deficiency
    BIOCHEMICAL

,

    Duchenne muscular dystrophy
    DIAGNOSIS

, and

    AHC
    DIAGNOSIS

.

adrenal insufficiency
hypogonadotropic hypogonadism
salt-losing adrenal crisis
adrenal insufficiency
adrenal crisis

AHC
aspiration pneumonia
Xp21 contiguous gene syndrome
AHC
Xp21 contiguous gene syndrome
Duchenne muscular dystrophy
AHC


Continuous infusion propofol general anesthesia for dental treatment in patients with progressive muscular dystrophy.

Progressive muscular dystrophy may produce abnormal reactions to several drugs. There is no consensus of opinion regarding the continuous infusion of propofol in patients with progressive muscular dystrophy. We successfully treated 2 patients with progressive muscular dystrophy who were anesthetized with a continuous infusion of propofol. In case 1, a 19-year-old, 59-kg man with Becker muscular dystrophy and mental retardation was scheduled for dental treatment under general anesthesia. General anesthesia was maintained by a continuous infusion of 6-10 mg/kg propofol per hour and an inhalational mixture of 67% nitrous oxide and 33% oxygen. No complications were observed during or after the operation. In case 2, a 5-year-old, 11-kg boy with Fukuyama type congenital muscular dystrophy and slight mental retardation was scheduled for dental treatment under general anesthesia. General anesthesia was maintained with a continuous infusion of 6-12 mg/kg propofol per hour and an inhalational mixture of 0.5-1.5% sevoflurane in 67% nitrous oxide and 33% oxygen. No complications were observed during or after the operation. It is speculated that a continuous infusion of propofol in progressive muscular dystrophy does not cause malignant hyperthermia because serum levels of creatine phosphokinase and myoglobin decreased after our anesthetic management. Furthermore, our observations suggest that sevoflurane may have some advantages in patients with progressive type muscular dystrophies other than Duchenne muscular dystrophy and Becker muscular dystrophy. In conclusion, our cases suggest that a continuous infusion of propofol for the patients with progressive muscular dystrophy is a safe component of our anesthetic strategy.

    Progressive muscular dystrophy
    DIAGNOSIS

 may produce

    abnormal reactions to several drugs
    SYMPTOMS

. There is no consensus of opinion regarding the

    continuous infusion of propofol
    MEDICATION

 in patients with

    progressive muscular dystrophy
    DIAGNOSIS

. We successfully treated 2 patients with

    progressive muscular dystrophy
    DIAGNOSIS

 who were

    anesthetized with a continuous infusion of propofol
    MEDICATION

. In case 1, a

    19-year-old
    AGE

,

    59-kg
    AGE

    man
    GENDER

 with

    Becker muscular dystrophy
    DIAGNOSIS

 and

    mental retardation
    SYMPTOMS

 was scheduled for

    dental treatment
    MEDICATION

 under

    general anesthesia
    MEDICATION

.

    General anesthesia
    MEDICATION

 was

    maintained by a continuous infusion of 6-10 mg/kg propofol per hour and an inhalational mixture of 67% nitrous oxide and 33% oxygen
    MEDICATION

.

    No complications were observed
    NEG_FINDINGS

 during or after the operation. In case 2, a

    5-year-old
    AGE

,

    11-kg boy
    AGE

 with

    Fukuyama type congenital muscular dystrophy
    DIAGNOSIS

 and

    slight mental retardation
    SYMPTOMS

 was scheduled for

    dental treatment under general anesthesia
    MEDICATION

.

    General anesthesia
    MEDICATION

 was

    maintained with a continuous infusion of 6-12 mg/kg propofol per hour and an inhalational mixture of 0.5-1.5% sevoflurane in 67% nitrous oxide and 33% oxygen
    MEDICATION

.

    No complications were observed
    NEG_FINDINGS

 during or after the

    operation
    MEDICATION

. It is speculated that a

    continuous infusion of propofol
    MEDICATION

 in

    progressive muscular dystrophy
    DIAGNOSIS

 does

    not cause malignant hyperthermia
    NEG_FINDINGS

 because

    serum levels of creatine phosphokinase and myoglobin decreased
    BIOCHEMICAL

 after

    our anesthetic management
    MEDICATION

. Furthermore, our observations suggest that

    sevoflurane
    MEDICATION

 may have some advantages in patients with

    progressive type muscular dystrophies
    DIAGNOSIS

 other than

    Duchenne muscular dystrophy
    DIAGNOSIS

 and

    Becker muscular dystrophy
    DIAGNOSIS

. In conclusion, our cases suggest that a

    continuous infusion of propofol
    MEDICATION

 for the patients with

    progressive muscular dystrophy
    DIAGNOSIS

 is a safe component of our anesthetic strategy.

abnormal reactions to several drugs
mental retardation
slight mental retardation

No complications were observed
No complications were observed
not cause malignant hyperthermia


Depressed left ventricular contractile reserve diagnosed by dobutamine stress echocardiography in a patient with Duchenne muscular dystrophy.

Cardiomyopathy is a leading cause of death in patients with Duchenne muscular dystrophy. Congestive heart failure is often sub-clinical and unrecognized as a result of the severe physical limitations of this patient population. We report the case of a 16-year-old boy with Duchenne muscular dystrophy who demonstrated normal left ventricular systolic function at rest by screening transthoracic echocardiogram. This patient, however, was noted to have depressed left ventricular contractile reserve by dobutamine stress echocardiography. Dobutamine stress echocardiography can have an important role in unmasking subclinical heart failure in this patient population.

    Cardiomyopathy
    DIAGNOSIS

 is a leading cause of

    death
    SYMPTOMS

 in patients with

    Duchenne muscular dystrophy
    DIAGNOSIS

.

    Congestive heart failure
    SYMPTOMS

 is often sub-clinical and unrecognized as a result of the

    severe physical limitations
    SYMPTOMS

 of this patient population. We report the case of a

    16-year-old
    AGE

    boy
    GENDER

 with

    Duchenne muscular dystrophy
    DIAGNOSIS

 who demonstrated

    normal left ventricular systolic function at rest
    NEG_FINDINGS

 by

    screening transthoracic echocardiogram
    PARACLINICAL

. This patient, however, was noted to have

    depressed left ventricular contractile reserve
    SYMPTOMS

 by

    dobutamine stress echocardiography
    PARACLINICAL

.

    Dobutamine stress echocardiography
    PARACLINICAL

 can have an important role in unmasking

    subclinical heart failure
    SYMPTOMS

 in this patient population.

Cardiomyopathy
Duchenne muscular dystrophy
Duchenne muscular dystrophy


Scoliosis in Steinert syndrome: a case report.

Steinert syndrome is described as an autosomal dominant condition characterized by progressive muscular wasting, myotonia, musculoskeletal manifestations and rare spinal defects. Little is reported about spinal deformity associated with this syndrome.

We present a patient with Steinert syndrome complicated by scoliosis. In the literature on muscular dystrophy, other than Duchenne, little mention is given to the problem of scoliosis in general and its treatment in particular.

A case report of a patient with Steinert syndrome associated with thoracic scoliosis and hypokyphosis is presented.

A 17-year-old boy presented with King type II right thoracic scoliosis (T5-T11, Cobb angle of 40 degrees) and hypokyphosis--10 degrees. He was treated with posterior stabilization and instrumentation at level T3-L2 with a postoperative correction of the scoliotic curve to 20 degrees. Histopathologic examination of the muscles confirmed the diagnosis of Steinert myotonic dystrophy.

At 30-month follow-up, the patient was clinically pain free and well balanced. Plain radiographs showed solid spine fusion with no loss of deformity correction.

Scoliosis in Steinert syndrome shares the characteristic of an arthrogrypotic neuromuscular curve and demands the extensive soft tissue release for optimal surgical correction. Intraoperative observations included profound tissue bleeding, abnormally tough soft tissues and a difficult recovery from anaesthesia.

    Steinert syndrome
    DIAGNOSIS

 is described as an

    autosomal dominant
    GENETICS

 condition characterized by

    progressive muscular wasting
    SYMPTOMS

,

    myotonia
    SYMPTOMS

,

    musculoskeletal manifestations
    SYMPTOMS

 and

    rare spinal defects
    SYMPTOMS

. Little is reported about

    spinal deformity
    SYMPTOMS

 associated with this syndrome.

We present a patient with

    Steinert syndrome
    DIAGNOSIS

 complicated by

    scoliosis
    DIAGNOSIS

. In the literature on

    muscular dystrophy
    DIAGNOSIS

, other than

    Duchenne
    DIAGNOSIS

, little mention is given to the problem of

    scoliosis
    DIAGNOSIS

 in general and its treatment in particular.

A case report of a patient with

    Steinert syndrome
    DIAGNOSIS

 associated with

    thoracic scoliosis
    SYMPTOMS

 and

    hypokyphosis
    SYMPTOMS

 is presented.

A

    17-year-old
    AGE

    boy
    GENDER

 presented with

    King type II right thoracic scoliosis (T5-T11, Cobb angle of 40 degrees)
    SYMPTOMS

 and

    hypokyphosis--10 degrees
    SYMPTOMS

.

    He
    GENDER

 was treated with

    posterior stabilization and instrumentation at level T3-L2
    MEDICATION

 with a

    postoperative correction of the scoliotic curve to 20 degrees
    MEDICATION

.

    Histopathologic examination of the muscles
    PARACLINICAL

 confirmed the diagnosis of

    Steinert myotonic dystrophy
    DIAGNOSIS

.

At

    30-month follow-up
    PARACLINICAL

, the patient was

    clinically pain free
    NEG_FINDINGS

 and

    well balanced
    SYMPTOMS

.

    Plain radiographs
    PARACLINICAL

 showed

    solid spine fusion
    SYMPTOMS

 with

    no loss of deformity correction
    NEG_FINDINGS

.

    Scoliosis
    DIAGNOSIS

 in

    Steinert syndrome
    DIAGNOSIS

 shares the

    characteristic of an arthrogrypotic neuromuscular curve
    SYMPTOMS

 and demands the

    extensive soft tissue release
    MEDICATION

 for

    optimal surgical correction
    MEDICATION

. Intraoperative observations included

    profound tissue bleeding
    SYMPTOMS

,

    abnormally tough soft tissues
    SYMPTOMS

 and a

    difficult recovery from anaesthesia
    NEG_FINDINGS

.

Steinert syndrome
Steinert syndrome
scoliosis
muscular dystrophy
Duchenne
scoliosis
Steinert syndrome
Steinert myotonic dystrophy
Scoliosis
Steinert syndrome

clinically pain free
no loss of deformity correction
difficult recovery from anaesthesia


[Delayed onset malignant hyperthermia after a closure of ventricular septal defect].

An 18 month-old girl was diagnosed as ventricular septal defect (VSD) with mild aortic valve prolapse. She underwent a closure of VSD. Intra-and early postoperative course was uneventful. However, 20 hours after surgery, sudden bradycardia led to cardiac arrest and strong muscle rigidity was seen. Hyperkalemia and metabolic acidosis rapidly progressed and resuscitation was failed. Extracorporeal life support and continuous hemodialysis were initiated, but the patient died with multiple organ failure on 5th postoperative day. Her clinical course supported the diagnosis of delayed onset malignant hyperthermia. Histopathological findings of muscle biopsy were consistent with rhabdomyolysis, and immunopathological stains demonstrated changes as in a Duchenne type muscular dystrophy carrier. Delayed onset malignant hyperthermia is an extremely rare complication of general anesthesia. We should be aware of this lethal condition, which occurs with a certain time lag after surgery, especially when the patient has possible background of myopathy.

An

    18 month-old
    AGE

    girl
    GENDER

 was diagnosed as

    ventricular septal defect (VSD)
    SYMPTOMS

 with

    mild aortic valve prolapse
    SYMPTOMS

.

    She
    GENDER

 underwent a

    closure of VSD
    MEDICATION

. Intra-and early postoperative course was

    uneventful
    NEG_FINDINGS

. However, 20 hours after

    surgery
    MEDICATION

,

    sudden bradycardia
    SYMPTOMS

 led to

    cardiac arrest
    SYMPTOMS

 and

    strong muscle rigidity
    SYMPTOMS

 was seen.

    Hyperkalemia
    BIOCHEMICAL

 and

    metabolic acidosis
    BIOCHEMICAL

 rapidly progressed and

    resuscitation was failed
    NEG_FINDINGS

.

    Extracorporeal life support and continuous hemodialysis
    MEDICATION

 were initiated, but the patient

    died
    SYMPTOMS

 with

    multiple organ failure
    SYMPTOMS

 on 5th postoperative day.

    Her
    GENDER

 clinical course supported the diagnosis of

    delayed onset malignant hyperthermia
    DIAGNOSIS

.

    Histopathological findings of muscle biopsy
    PARACLINICAL

 were consistent with

    rhabdomyolysis
    DIAGNOSIS

, and

    immunopathological stains
    PARACLINICAL

 demonstrated

    changes as in
    MICROSCOPIC

 a

    Duchenne type muscular dystrophy carrier
    DIAGNOSIS

.

    Delayed onset malignant hyperthermia
    DIAGNOSIS

 is an extremely rare complication of

    general anesthesia
    MEDICATION

. We should be aware of this lethal condition, which occurs with a certain time lag after

    surgery
    MEDICATION

, especially when the patient has possible background of

    myopathy
    DIAGNOSIS

.

ventricular septal defect (VSD)
mild aortic valve prolapse
sudden bradycardia
cardiac arrest
strong muscle rigidity
died
multiple organ failure


Hyperkalemic cardiac arrest after cardiopulmonary bypass in a child with unsuspected duchenne muscular dystrophy.

Adverse reactions to volatile anesthetics and depolarizing muscle relaxants can occur in patients with Duchenne muscular dystrophy (DMD) resulting in acute rhabdomyolysis and hyperkalemia. We report a case of hyperkalemic cardiac arrest after cardiac surgery using cardiopulmonary bypass in a child with unsuspected DMD. Early diagnosis and management of hyperkalemia resulted in a successful outcome. Genetic testing confirmed the diagnosis of DMD. We recommend a thorough preoperative investigation, including creatine kinase estimation, in children with a history of unexplained motor delay.

    Adverse reactions to volatile anesthetics
    SYMPTOMS

 and

    depolarizing muscle relaxants
    MEDICATION

 can occur in patients with

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 resulting in

    acute rhabdomyolysis
    SYMPTOMS

 and

    hyperkalemia
    BIOCHEMICAL

. We report a case of

    hyperkalemic cardiac arrest
    SYMPTOMS

 after

    cardiac surgery using cardiopulmonary bypass
    MEDICATION

 in a

    child
    AGE

 with

    unsuspected DMD
    NEG_FINDINGS

. Early diagnosis and management of

    hyperkalemia
    BIOCHEMICAL

 resulted in a successful outcome.

    Genetic testing
    PARACLINICAL

 confirmed the diagnosis of

    DMD
    DIAGNOSIS

. We recommend a

    thorough preoperative investigation
    PARACLINICAL

, including

    creatine kinase estimation
    PARACLINICAL

, in

    children
    AGE

 with a history of

    unexplained motor delay
    SYMPTOMS

.


[Clinical pathologic studies and genetic analysis of a female Duchenne muscular dystrophy family].

To investigate the clinical features of female Duchenne muscular dystrophy(DMD), and find out the onset mechanism.

The clinical manifestations of a female DMD family were followed; the immunofluorescence studies on muscle system and the genetic analysis were carried out.

The clinical manifestations and results of relevant examinations on the DMD woman in this family were in accordance with the typical characteristics of DMD. The 39-year-old mother of this proband was noted to have a clinical feature resembling that of Becker muscular dystrophy (BMD), and the immunofluorescence analysis revealed that dystrophin positive fibers and negative fibers co-existed in her muscle. The dystrophy genetic analysis of the family indicated non-deletions. The mother's karyotype was found to be normal.

The 39-year-old female patient's clinical manifestations were similar to BMD, and only one third of her fibers were dystrophin-positive. The present authors assume that the skewed pattern of X inactivation is the likely mechanism, because the karyotype is normal.

To investigate the clinical features of

    female
    GENDER

    Duchenne muscular dystrophy(DMD)
    DIAGNOSIS

, and find out the onset mechanism.

The clinical manifestations of a

    female
    GENDER

    DMD
    DIAGNOSIS

 family were followed; the

    immunofluorescence studies on muscle system
    PARACLINICAL

 and the

    genetic analysis
    PARACLINICAL

 were carried out.

The clinical manifestations and results of relevant examinations on the

    DMD
    DIAGNOSIS

    woman
    GENDER

 in this family were in accordance with the typical characteristics of

    DMD
    DIAGNOSIS

. The

    39-year-old
    AGE

    mother
    GENDER

 of this

    proband
    GENDER

 was noted to have a

    clinical feature resembling that of Becker muscular dystrophy (BMD)
    SYMPTOMS

, and the

    immunofluorescence analysis
    PARACLINICAL

 revealed that

    dystrophin positive fibers and negative fibers co-existed in her muscle
    MICROSCOPIC

. The

    dystrophy genetic analysis of the family
    PARACLINICAL

 indicated

    non-deletions
    GENETICS

. The

    mother's karyotype was found to be normal
    NEG_FINDINGS

.

The

    39-year-old
    AGE

    female
    GENDER

 patient's

    clinical manifestations were similar to BMD
    SYMPTOMS

, and

    only one third of her fibers were dystrophin-positive
    MICROSCOPIC

. The present authors assume that the

    skewed pattern of X inactivation
    GENETICS

 is the likely mechanism, because the

    karyotype is normal
    NEG_FINDINGS

.

Duchenne muscular dystrophy(DMD)
DMD
DMD
DMD

non-deletions
skewed pattern of X inactivation


Complex glycerol kinase deficiency: an X-linked disorder associated with adrenal hypoplasia congenita.

Complex glycerol kinase deficiency (GKD) results from the contiguous deletion on Xp21 of all or part of the gene for glycerol kinase together with that for adrenal hypoplasia congenita (AHC) and /or Duchenne muscular dystrophy (DMD). The authors present the case of a newborn whose initial issues were refractory hypoglycaemia along with hyponatremia and hyperkalemia. He also had low serum cortisol levels and raised urinary excretion of glycerol and required steroid supplementation. His creatinine phosphokinase (CPK) levels were normal. Molecular studies revealed a contiguous Xp21 deletion. Therapy in such cases must be prompt and includes correction of hypoglycaemia and dyselectrolytemia, a low fat diet and steroid replacement.

    Complex glycerol kinase deficiency (GKD)
    DIAGNOSIS

 results from the

    contiguous deletion on Xp21 of all or part of the gene for glycerol kinase
    GENETICS

 together with that for

    adrenal hypoplasia congenita (AHC)
    DIAGNOSIS

 and /or

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

. The authors present the case of a

    newborn
    AGE

 whose initial issues were

    refractory hypoglycaemia
    BIOCHEMICAL

 along with

    hyponatremia
    BIOCHEMICAL

 and

    hyperkalemia
    BIOCHEMICAL

.

    He
    GENDER

 also had

    low serum cortisol levels
    BIOCHEMICAL

 and

    raised urinary excretion of glycerol
    BIOCHEMICAL

 and required

    steroid supplementation
    MEDICATION

.

    His
    GENDER

    creatinine phosphokinase (CPK) levels were normal
    NEG_FINDINGS

.

    Molecular studies
    PARACLINICAL

 revealed a

    contiguous Xp21 deletion
    GENETICS

. Therapy in such cases must be prompt and includes

    correction of hypoglycaemia
    MEDICATION

 and

    dyselectrolytemia
    BIOCHEMICAL

, a

    low fat diet
    MEDICATION

 and

    steroid replacement
    MEDICATION

.

refractory hypoglycaemia
hyponatremia
hyperkalemia
low serum cortisol levels
raised urinary excretion of glycerol
dyselectrolytemia

steroid supplementation
correction of hypoglycaemia
low fat diet
steroid replacement


Anaesthetic management during labour of a manifesting carrier of Duchenne muscular dystrophy.

We describe the peripartum anaesthetic management of a 36-year-old woman who was a manifesting carrier of Duchenne muscular dystrophy. Duchenne muscular dystrophy is an X-linked recessive disorder affecting young males associated with severe complications during anaesthesia if depolarising neuromuscular blocking drugs and volatile agents are used. A manifesting carrier is a heterozygous female who demonstrates the disease in a milder form than in males. This probably occurs because of skewed X-inactivation. We planned to establish regional anaesthesia should an operation be necessary during labour or delivery and to use propofol total intravenous anaesthesia and rocuronium if general anaesthesia became unavoidable. At 37 weeks, the woman went into spontaneous labour, but fetal distress necessitated caesarean section for which combined spinal-epidural anaesthesia was used.

We describe the

    peripartum anaesthetic management
    MEDICATION

 of a

    36-year-old
    AGE

    woman
    GENDER

 who was a manifesting carrier of

    Duchenne muscular dystrophy
    DIAGNOSIS

.

    Duchenne muscular dystrophy
    DIAGNOSIS

 is an

    X-linked recessive disorder
    GENETICS

 affecting

    young
    AGE

    males
    GENDER

 associated with

    severe complications
    SYMPTOMS

 during

    anaesthesia
    MEDICATION

 if

    depolarising neuromuscular blocking drugs and volatile agents
    MEDICATION

 are used. A manifesting carrier is a

    heterozygous
    GENETICS

    female
    GENDER

 who demonstrates the disease in a milder form than in

    males
    GENDER

. This probably occurs because of

    skewed X-inactivation
    GENETICS

. We planned to establish

    regional anaesthesia
    MEDICATION

 should an

    operation
    MEDICATION

 be necessary during

    labour or delivery
    MEDICATION

 and to use

    propofol total intravenous anaesthesia and rocuronium
    MEDICATION

 if

    general anaesthesia became unavoidable
    NEG_FINDINGS

. At

    37 weeks
    MEDICATION

, the

    woman
    GENDER

    went into spontaneous labour
    MEDICATION

, but

    fetal distress
    SYMPTOMS

 necessitated

    caesarean section
    MEDICATION

 for which

    combined spinal-epidural anaesthesia
    MEDICATION

 was used.

Duchenne muscular dystrophy
Duchenne muscular dystrophy

X-linked recessive disorder
heterozygous
skewed X-inactivation