[Postmortem diagnosis of Fabry disease in a female heterozygote leading to the detection of undiagnosed manifest disease in the family].

The authors detected on necropsy in a 63-year-old woman with the clinical diagnosis of hypertension, atherosclerosis of the coronary and peripheral arteries, thromboembolism into the cerebral circulation and impaired cardiac conductivity lysosomal storage identified by histochemical and electronoptic analyses along with lipid chromatography as Fabry's disease. The stored lipids were neutral glycosphingolipids of the globo series globotriaosylceramide) and of the gala- series (galabiosylceramide) which accumulated as a result of deficient activity of the degrading enzyme alpha galactosidase A. Marked accumulation of these specific lipids was found in cardiomyocytes, in smooth muscles (of the media in arteries of the heart, kidneys, liver, spleen, lungs) in podocytes and mesangial cells of renal glomeruli, in epithelia of Henle's loop and in the distal tubules. In the vascular endothelium the storage was at the borderline of detectability. Accumulation did not lead to detectable organ disorders with the exception of the heart where it participated, no doubt, significantly in the cardiocyte hypertrophy. Examination of relatives revealed in the proband's son (age 41 years) a combination of renal, cardiac and skin changes typical for Fabry's disease which, however was not clinically diagnosed. The diagnosis was confirmed by proving of alpha-galactosidase A deficiency in the peripheral leucocytes and point mutation L293X in the VIth exon of the appropriate gene. In a granddaughter (age 15 years) biochemical and molecular genetic methods revealed the heterozygous state of Fabry's disease in preclinical stage.

The authors detected on

    necropsy
    PARACLINICAL

 in a

    63-year-old
    AGE

    woman
    GENDER

 with the clinical diagnosis of

    hypertension
    SYMPTOMS

,

    atherosclerosis of the coronary and peripheral arteries
    SYMPTOMS

,

    thromboembolism into the cerebral circulation
    SYMPTOMS

 and

    impaired cardiac conductivity
    SYMPTOMS

    lysosomal storage
    MICROSCOPIC

 identified by

    histochemical and electronoptic analyses
    PARACLINICAL

 along with

    lipid chromatography
    PARACLINICAL

 as

    Fabry's disease
    DIAGNOSIS

.

    The stored lipids were neutral glycosphingolipids of the globo series globotriaosylceramide) and of the gala- series (galabiosylceramide) which accumulated
    MICROSCOPIC

 as a result of deficient activity of the degrading enzyme alpha galactosidase A.

    Marked accumulation of these specific lipids was found in cardiomyocytes, in smooth muscles (of the media in arteries of the heart, kidneys, liver, spleen, lungs) in podocytes and mesangial cells of renal glomeruli, in epithelia of Henle's loop and in the distal tubules
    MICROSCOPIC

.

    In the vascular endothelium the storage was at the borderline of detectability
    MICROSCOPIC

.

    Accumulation did not lead to detectable organ disorders
    MICROSCOPIC

 with the exception of the

    heart
    SYMPTOMS

 where it participated, no doubt, significantly in the

    cardiocyte hypertrophy
    SYMPTOMS

.

    Examination of relatives
    PARACLINICAL

 revealed

    in the proband's son (age 41 years
    FAMILY

    ) a combination of renal, cardiac and skin changes typical for Fabry's disease
    FAMILY

 which, however

    was not clinically diagnosed
    NEG_FINDINGS

. The diagnosis was confirmed by proving of

    alpha-galactosidase A deficiency in the peripheral leucocytes
    BIOCHEMICAL

 and

    point mutation L293X in the VIth exon of the appropriate gene
    GENETICS

. In a

    granddaughter (age 15 years
    FAMILY

)

    biochemical and molecular genetic methods
    PARACLINICAL

 revealed the

    heterozygous state of Fabry's disease in preclinical stage
    GENETICS

.


[Fabry's disease--late diagnosis in men with chronic nephropathy and skin changes].

We report a case of Fabry's disease, diagnosed in a 39-year-old patient treated for 4 years because of glomerulonephritis. The disease manifested itself by the presence of typical petechiae-like skin lesions in the bathing trunk area (angiokeratoma), eye changes, paresthesia, and--in additional investigations--mild proteinuria, lowered creatinine clearance, along with changes in the central nervous system. A biopsy of the kidney revealed the presence of foamy cells in all glomeruli, and in electron microscopy multilamellar bodies (zebra bodies). The diagnose of the disease was confirmed by a marked decrease in leucocyte alpha-galactosidase activity. An early diagnosis of non-inflammatory character of Fabry's disease allows to avoid an unnecessary immunosuppressive treatment.

We report a case of

    Fabry's disease
    DIAGNOSIS

, diagnosed in a

    39-year-old
    AGE

 patient

    treated for 4 years
    MEDICATION

 because of

    glomerulonephritis
    DIAGNOSIS

. The disease manifested itself by the presence of

    typical petechiae-like skin lesions in the bathing trunk area (angiokeratoma)
    SYMPTOMS

,

    eye changes
    SYMPTOMS

,

    paresthesia
    SYMPTOMS

, and--in additional investigations--

    mild proteinuria
    BIOCHEMICAL

,

    lowered creatinine clearance
    BIOCHEMICAL

, along with

    changes in the central nervous system
    SYMPTOMS

. A

    biopsy of the kidney
    PARACLINICAL

 revealed the

    presence of foamy cells in all glomeruli
    MICROSCOPIC

, and in

    electron microscopy
    PARACLINICAL

    multilamellar bodies (zebra bodies)
    MICROSCOPIC

. The diagnose of the disease was confirmed by a

    marked decrease in leucocyte alpha-galactosidase activity
    BIOCHEMICAL

. An early diagnosis of

    non-inflammatory character of Fabry's disease
    DIAGNOSIS

 allows to

    avoid an unnecessary immunosuppressive treatment
    NEG_FINDINGS

.


[High-flow priapism in the pediatric age: review].

To review the literature on high flow priapism in children and analyze the etiology, pathophysiological mechanism, diagnostic tests, treatment and complications.

The literature is reviewed and an additional case of posttraumatic arterial priapism in an 11 year-old boy treated at our hospital is presented.

24 cases of high flow priapism in children were found; 18 had a history of genitoperineal trauma, 5 had sickle cell anemia and one child had Fabry's disease. Diagnosis was based on patient history, intracavernous blood gases and echo doppler findings. Fourteen patients with posttraumatic priapism, one patient with sickle cell anemia and the child with Fabry's disease were treated by pudendal arteriography with embolization. The immediate results and erectile function were good.

Genitoperineal trauma is the most common cause of arterial priapism in children. High flow must be considered in children with sickle cell disease and priapism that do not respond to conventional treatment. Pudendal arteriography with embolization is the treatment of choice. Erectile function is recovered after treatment.

To review the literature on

    high flow priapism
    SYMPTOMS

 in

    children
    AGE

 and analyze the etiology, pathophysiological mechanism, diagnostic tests, treatment and complications.

The literature is reviewed and an additional case of

    posttraumatic arterial priapism
    SYMPTOMS

 in an

    11 year-old
    AGE

    boy
    GENDER

 treated at our hospital is presented.

24 cases of

    high flow priapism
    SYMPTOMS

 in

    children
    AGE

 were found; 18 had a

    history of genitoperineal trauma
    SYMPTOMS

, 5 had

    sickle cell anemia
    DIAGNOSIS

 and one

    child
    AGE

 had

    Fabry's disease
    DIAGNOSIS

. Diagnosis was based on patient history,

    intracavernous blood gases
    PARACLINICAL

 and

    echo doppler findings
    PARACLINICAL

. Fourteen patients with

    posttraumatic priapism
    SYMPTOMS

, one patient with

    sickle cell anemia
    DIAGNOSIS

 and the

    child
    AGE

 with

    Fabry's disease
    DIAGNOSIS

 were treated by

    pudendal arteriography with embolization
    MEDICATION

. The immediate results and

    erectile function were good
    SYMPTOMS

.

    Genitoperineal trauma
    SYMPTOMS

 is the most common cause of

    arterial priapism
    SYMPTOMS

 in

    children
    AGE

.

    High flow
    SYMPTOMS

 must be considered in

    children
    AGE

 with

    sickle cell disease
    DIAGNOSIS

 and

    priapism
    SYMPTOMS

 that

    do not respond to conventional treatment
    NEG_FINDINGS

.

    Pudendal arteriography
    PARACLINICAL

 with

    embolization
    MEDICATION

 is the treatment of choice.

    Erectile function is recovered
    SYMPTOMS

 after treatment.

high flow priapism
posttraumatic arterial priapism
high flow priapism
history of genitoperineal trauma
posttraumatic priapism
erectile function were good
Genitoperineal trauma
arterial priapism
High flow
priapism
Erectile function is recovered

sickle cell anemia
Fabry's disease
sickle cell anemia
Fabry's disease
sickle cell disease


Biopsy-proven cardiomyopathy in heterozygous Fabry's disease.

A 23-year-old woman with heterozygous Fabry's disease who had acroparesthesia was admitted to hospital for precise examination of the disease before childbearing. She had no cardiac-related symptoms and no abnormality on physical examination. The alpha-galactosidase A activity in her leukocytes was present, but lower than normal. However, the endomyocardial biopsy showed specific changes for Fabry's disease. As Fabry's disease is a rare X-linked recessive inborn error of glycosphingolipid metabolism, heterozygous females are usually asymptomatic, but rarely can be affected as severely as hemizygous males. This is an isolated case of heterozygous Fabry's disease in a female in whom cardiac involvement was detected by endomyocardial biopsy, although she had no cardiac abnormality on physiological examinations. In conclusion, endomyocardial biopsy is useful for evaluation of the cardiac involvement of Fabry's disease even in an asymptomatic case.

A

    23-year-old
    AGE

    woman
    GENDER

 with

    heterozygous Fabry's disease
    DIAGNOSIS

 who had

    acroparesthesia
    SYMPTOMS

 was admitted to hospital for precise examination of the disease before

    childbearing
    AGE

.

    She
    GENDER

 had

    no cardiac-related symptoms
    NEG_FINDINGS

 and

    no abnormality on physical examination
    NEG_FINDINGS

.

    The alpha-galactosidase A activity in her leukocytes was present, but lower than normal
    BIOCHEMICAL

. However, the

    endomyocardial biopsy
    PARACLINICAL

 showed

    specific changes for Fabry's disease
    MICROSCOPIC

. As

    Fabry's disease
    DIAGNOSIS

 is a

    rare X-linked recessive inborn error of glycosphingolipid metabolism
    GENETICS

,

    heterozygous
    GENETICS

    females
    GENDER

 are usually

    asymptomatic
    NEG_FINDINGS

, but rarely can be affected as severely as

    hemizygous males
    GENETICS

. This is an isolated case of

    heterozygous Fabry's disease
    DIAGNOSIS

 in a

    female
    GENDER

 in whom

    cardiac involvement
    SYMPTOMS

 was detected by

    endomyocardial biopsy
    PARACLINICAL

, although

    she
    GENDER

 had

    no cardiac abnormality on physiological examinations
    NEG_FINDINGS

. In conclusion,

    endomyocardial biopsy
    PARACLINICAL

 is useful for evaluation of the

    cardiac involvement
    SYMPTOMS

 of

    Fabry's disease
    DIAGNOSIS

 even in an

    asymptomatic
    NEG_FINDINGS

 case.

heterozygous Fabry's disease
Fabry's disease
heterozygous Fabry's disease
Fabry's disease

acroparesthesia
cardiac involvement
cardiac involvement


Dynamic left ventricular arterial pressure gradient and sick sinus syndrome with heterozygous Fabry's disease improved following implantation of a dual chamber pacemaker.

A 63-year-old woman with heterozygous Fabry's disease, sick sinus syndrome, sinus pauses, congestive heart failure, syncope, and a dynamic pressure gradient between the left ventricle and systemic arteries underwent implantation of a dual chamber (DDD) pacemaker. Following pacemaker implantation, the pressure gradient has been reduced and congestive heart failure controlled for the past 3 years.

A

    63-year-old
    AGE

    woman
    GENDER

 with

    heterozygous Fabry's disease
    GENETICS

,

    sick sinus syndrome
    SYMPTOMS

,

    sinus pauses
    SYMPTOMS

,

    congestive heart failure
    SYMPTOMS

,

    syncope
    SYMPTOMS

, and a

    dynamic pressure gradient between the left ventricle and systemic arteries
    SYMPTOMS

 underwent

    implantation of a dual chamber (DDD) pacemaker
    MEDICATION

. Following

    pacemaker implantation
    MEDICATION

, the

    pressure gradient has been reduced
    SYMPTOMS

 and

    congestive heart failure controlled for the past 3 years
    SYMPTOMS

.


[A case of Fabry's disease with chronic renal failure].

Fabry's disease is a genetic disorder caused by the absence of alpha-galactosidase (alpha-Gal), the gene of which is carried on the long arm of the X chromosome. This enzymatic defect leads to an accumulation of glycosphingolipids in the plasma and lysosomes of endothelial, perithelial, and smooth muscle cells, especially involving those of the cardiovascular, renal and cerebrovascular systems. We report one male case of Fabry's disease with renal deterioration. A 36-year-old man who was a classic case with acroparesthesia, angiokeratoma, and hypohidrosis from 10 years of age, was diagnosed to be a hemizygote of Fabry's disease at 27 years as a result of severe decreased alpha-Gal activity of his peripheral white blood cells. This patient was found to have a point mutation of a G to A transition in exon 1. In May, 1989, he was reported to have proteinuria with normal renal function and admitted to our hospital due to renal deterioration in September, 1993. Laboratory examinations revealed a serum urea nitrogen of 65 mg/dl and creatinine value of 6.9 mg/dl. Urinary protein excretion was 3.9 g/day and urinary sugar was negative. On the renal biopsy specimens, light microscopic examinations revealed multiple sclerosing and collaptic lesions in glomeruli without severe tubulo-interstitial damage, but with stenotic change of the small arteries and arterioles. Electron microscopic examinations revealed a large number of electron dense deposits in the tubules. We diagnosed this case as Fabry's disease with chronic renal failure, however the pathogenesis of this renal progressive deterioration remained obscure. In this case, degenerative changes in the renal vessels due to Fabry's disease may be associated with rapid deterioration in renal function.

    Fabry's disease
    DIAGNOSIS

 is a

    genetic disorder
    GENETICS

 caused by the

    absence of alpha-galactosidase (alpha-Gal)
    BIOCHEMICAL

    , the gene of which is carried on the long arm of the X chromosome
    GENETICS

. This

    enzymatic defect
    BIOCHEMICAL

 leads to an

    accumulation of glycosphingolipids in the plasma and lysosomes of endothelial, perithelial, and smooth muscle cells, especially involving those of the cardiovascular, renal and cerebrovascular systems
    MICROSCOPIC

. We report one

    male
    GENDER

 case of

    Fabry's disease
    DIAGNOSIS

 with

    renal deterioration
    SYMPTOMS

. A

    36-year-old
    AGE

    man
    GENDER

 who was a classic case with

    acroparesthesia
    SYMPTOMS

,

    angiokeratoma
    SYMPTOMS

, and

    hypohidrosis
    SYMPTOMS

    from 10 years of age
    AGE

, was diagnosed to be a

    hemizygote of Fabry's disease
    GENETICS

    at 27 years
    AGE

 as a result of

    severe decreased alpha-Gal activity of his peripheral white blood cells
    BIOCHEMICAL

. This patient was found to have a

    point mutation of a G to A transition in exon 1
    GENETICS

. In May, 1989,

    he
    GENDER

 was reported to have

    proteinuria
    BIOCHEMICAL

 with

    normal renal function
    NEG_FINDINGS

 and admitted to our hospital due to

    renal deterioration
    SYMPTOMS

 in September, 1993.

    Laboratory examinations
    PARACLINICAL

 revealed a

    serum urea nitrogen of 65 mg/dl
    BIOCHEMICAL

 and

    creatinine value of 6.9 mg/dl
    BIOCHEMICAL

.

    Urinary protein excretion was 3.9 g/day
    BIOCHEMICAL

 and

    urinary sugar was negative
    NEG_FINDINGS

. On the

    renal biopsy specimens
    PARACLINICAL

,

    light microscopic examinations
    PARACLINICAL

 revealed

    multiple sclerosing and collaptic lesions in glomeruli
    MICROSCOPIC

    without severe tubulo-interstitial damage
    NEG_FINDINGS

, but with

    stenotic change of the small arteries and arterioles
    SYMPTOMS

.

    Electron microscopic examinations
    PARACLINICAL

 revealed a

    large number of electron dense deposits in the tubules
    MICROSCOPIC

. We diagnosed this case as

    Fabry's disease
    DIAGNOSIS

 with

    chronic renal failure
    DIAGNOSIS

, however the pathogenesis of this

    renal progressive deterioration
    SYMPTOMS

 remained obscure. In this case,

    degenerative changes in the renal vessels
    SYMPTOMS

 due to

    Fabry's disease
    DIAGNOSIS

 may be associated with

    rapid deterioration in renal function
    SYMPTOMS

.

Fabry's disease
Fabry's disease
Fabry's disease
chronic renal failure
Fabry's disease


Acute anterior forearm compartment syndrome following wrist arthrodesis.

The authors report a case of anterior compartment syndrome in the forearm following total wrist arthrodesis via a dorsal approach. As far as they know this is the second case reported.

The authors report a case of

    anterior compartment syndrome in the forearm
    SYMPTOMS

 following

    total wrist arthrodesis via a dorsal approach
    MEDICATION

. As far as they know this is the second case reported.


The ultrastructural changes in renal biopsy compatible with Fabry's disease. Case report.

The authors reported the accumulation of osmiophilic myelin-like bodies typical for Fabry's disease in the rebiopsied 19-year-old woman clinically presenting with intermittent mild microhematuria and trace proteinuria. The light microscopy examination of the first kidney biopsy specimen (10 years ago) showed the presence of vacuolated cells in glomeruli, but electron microscopy study was not performed. The family history was negative for renal diseases. A biochemical enzymatic assay for alpha-galactosidase A was not performed. It is concluded that electron microscopy examination of kidney biopsy specimen is important for the investigation of storage diseases.

The authors reported the

    accumulation of osmiophilic myelin-like bodies typical for Fabry's disease
    MICROSCOPIC

 in the rebiopsied

    19-year-old
    AGE

    woman
    GENDER

 clinically presenting with

    intermittent mild microhematuria
    BIOCHEMICAL

 and

    trace proteinuria
    BIOCHEMICAL

. The

    light microscopy examination of the first kidney biopsy specimen
    PARACLINICAL

 (10 years ago) showed the

    presence of vacuolated cells in glomeruli
    MICROSCOPIC

, but

    electron microscopy study
    PARACLINICAL

    was not performed
    NEG_FINDINGS

. The

    family history was negative for renal diseases
    NEG_FINDINGS

.

    A biochemical enzymatic assay for alpha-galactosidase A was not performed
    NEG_FINDINGS

. It is concluded that

    electron microscopy examination of kidney biopsy specimen
    PARACLINICAL

 is important for the investigation of

    storage diseases
    DIAGNOSIS

.

intermittent mild microhematuria
trace proteinuria


Fabry's disease. Report of the case diagnosed on the basis of routine ultrastructural examination of the renal biopsy.

A 45-year-old man who developed proteinuria was diagnosed as having Fabry's disease on the basis of renal histological findings and prominent decreases in alpha-galactosidase A activity in blood leukocytes.

A

    45-year-old
    AGE

    man
    GENDER

 who developed

    proteinuria
    BIOCHEMICAL

 was diagnosed as having

    Fabry's disease
    DIAGNOSIS

 on the basis of

    renal histological findings
    PARACLINICAL

 and

    prominent decreases in alpha-galactosidase A activity in blood leukocytes
    BIOCHEMICAL

.


Fifteen-year follow-up of a heterozygous Fabry's disease patient associated with pre-excitation syndrome.

A 47-year-old woman with heterozygous Fabry's disease with pre-excitation syndrome has been followed up for 15 years. Diagnosis was confirmed by the typical electron microscopic feature of the endomyocardial specimen and a decreased plasma alpha-galactosidase activity. As the disease progressed, the interventricular septum thickened from 11 to 17 mm as measured by echocardiography, while the AH interval was prolonged from 80 to 140 msec. In Fabry's disease, the PR interval has been reported to be variable from short PR to AV block. Therefore, this case may be helpful to understand the time course in the AV conduction abnormalities with the progression of Fabry's disease.

A

    47-year-old
    AGE

    woman
    GENDER

 with

    heterozygous Fabry's disease
    DIAGNOSIS

 with

    pre-excitation syndrome
    SYMPTOMS

 has been followed up for 15 years. Diagnosis was confirmed by the typical

    electron microscopic feature of the endomyocardial specimen
    PARACLINICAL

 and a

    decreased plasma alpha-galactosidase activity
    BIOCHEMICAL

. As the disease progressed,

    the interventricular septum thickened from 11 to 17 mm
    SYMPTOMS

 as measured by

    echocardiography
    PARACLINICAL

, while the

    AH interval was prolonged from 80 to 140 msec
    SYMPTOMS

. In

    Fabry's disease
    DIAGNOSIS

, the

    PR interval
    SYMPTOMS

 has been reported to be

    variable from short PR to AV block
    SYMPTOMS

. Therefore, this case may be helpful to understand the time course in the

    AV conduction abnormalities
    SYMPTOMS

 with the progression of

    Fabry's disease
    DIAGNOSIS

.

heterozygous Fabry's disease
Fabry's disease
Fabry's disease


Cardiac variant of Fabry's disease mimicking hypertrophic cardiomyopathy.

A case of cardiac variant of Fabry's disease mimicking hypertrophic cardiomyopathy is reported. The diagnosis was obtained by biventricular endomyocardial biopsy showing severely hypertrophied myocardiocytes with large periodic acid-Schiff and Sudan black positive perinuclear vacuoles, shown at electromicroscopy to consist of lamellated cytoplasmic figures highly suggestive of Fabry's disease, and confirmed by diagnostic low activity of alpha-galactosidase A in the peripheral lymphocytes. Invasive approach was suggested by the occurrence of a long-standing atrial fibrillation that failed to determine deterioration of cardiac function. Differential diagnosis between hypertrophic cardiomyopathy and the cardiac variant of Fabry's disease is relevant for prognostic and therapeutic implications including the perspective of an enzyme replacement therapy.

A case of

    cardiac variant of Fabry's disease mimicking hypertrophic cardiomyopathy
    DIAGNOSIS

 is reported. The diagnosis was obtained by

    biventricular endomyocardial biopsy
    PARACLINICAL

 showing

    severely hypertrophied myocardiocytes with large periodic acid-Schiff and Sudan black positive perinuclear vacuoles
    MICROSCOPIC

, shown at

    electromicroscopy
    PARACLINICAL

    to consist of lamellated cytoplasmic figures highly suggestive of Fabry's disease
    MICROSCOPIC

, and confirmed by diagnostic

    low activity of alpha-galactosidase A in the peripheral lymphocytes
    BIOCHEMICAL

. Invasive approach was suggested by the occurrence of a

    long-standing atrial fibrillation
    SYMPTOMS

 that

    failed to determine deterioration of cardiac function
    NEG_FINDINGS

.

    Differential diagnosis
    PARACLINICAL

 between

    hypertrophic cardiomyopathy
    DIAGNOSIS

 and the

    cardiac variant of Fabry's disease
    DIAGNOSIS

 is relevant for prognostic and therapeutic implications including the perspective of an

    enzyme replacement therapy
    MEDICATION

.


Different phenotypic expression in relatives with fabry disease caused by a W226X mutation.

Two male relatives with Fabry disease presented striking differences in clinical symptoms and age of onset. The propositus had retarded statural growth and skeletal dysplasia while his nephew suffered mainly from aggravating acroparesthesia and celiac disease. Fabry disease is an X-linked inborn error of glycosphingolipid metabolism resulting from deficient activity of the lysosomal hydrolase alpha-galactosidase A (alpha-Gal A) enzyme. The alpha-Gal A gene is located at Xq22.1. Efforts to establish genotype-phenotype correlations have been limited because most patients have private mutations. In previous clinical studies performed in families with Fabry disease, marked differences in phenotype are described between affected relatives. This family also demonstrates the difficulty in predicting the clinical phenotype in patients and relatives with the same alpha-Gal A mutation. Furthermore, in the absence of a family history, the diagnosis may be easily missed.

Two

    male
    GENDER

    relatives with Fabry disease
    FAMILY

 presented striking differences in clinical symptoms and age of onset. The

    propositus had retarded statural growth
    FAMILY

 and

    skeletal dysplasia
    SYMPTOMS

 while

    his
    GENDER

    nephew suffered mainly from aggravating acroparesthesia and celiac disease
    FAMILY

.

    Fabry disease
    DIAGNOSIS

 is an

    X-linked
    GENETICS

    inborn error of glycosphingolipid metabolism
    DIAGNOSIS

 resulting from

    deficient activity of the lysosomal hydrolase alpha-galactosidase A (alpha-Gal A) enzyme
    BIOCHEMICAL

.

    The alpha-Gal A gene is located at Xq22.1
    GENETICS

. Efforts to establish genotype-phenotype correlations have been limited because most patients have

    private mutations
    GENETICS

. In previous clinical studies performed in families with

    Fabry disease
    DIAGNOSIS

,

    marked differences in
    FAMILY

 phenotype are described

    between affected relatives
    FAMILY

. This family also demonstrates the difficulty in predicting the clinical phenotype in patients and

    relatives with the same alpha-Gal A mutation
    FAMILY

. Furthermore, in the absence of a family history, the diagnosis may be easily missed.


[Retinal pigment anomalies associated with Fabry's disease].

Fabry's disease is an X linked disease with ocular, skin and kidney lesions. We report a case which presented all the ophthalmologic signs and particular retinal manifestations.

Fabry's disease was suspected in a 18 year old young man, with angiokeratomes, attacks of pain located in fingers, toes and also in the abdomen. Typical ocular morphological findings, namely whorl-like corneal opacities, posterior spoke-like cataracts and tortuosity of conjunctival vessels were found. His mother had the same ocular signs. The patient was also examined with fluorescein fundus angiography.

The diagnostic value of the ocular abnormalities can be significant and are very indicative of the disease in hemizygous and heterozygous patients. Except the retinal vascular tortuosity, we describe peripheric abnormalities of the retinal pigment epithelium suggesting another disease finding.

    Fabry's disease
    DIAGNOSIS

 is an

    X linked disease
    GENETICS

 with

    ocular, skin and kidney lesions
    SYMPTOMS

. We report a case which presented

    all the ophthalmologic signs
    SYMPTOMS

 and

    particular retinal manifestations
    SYMPTOMS

.

    Fabry's disease
    DIAGNOSIS

 was suspected in a

    18 year old
    AGE

    young
    AGE

    man
    GENDER

, with

    angiokeratomes
    SYMPTOMS

,

    attacks of pain located in fingers, toes and also in the abdomen
    SYMPTOMS

. Typical

    ocular morphological findings
    SYMPTOMS

, namely

    whorl-like corneal opacities
    SYMPTOMS

,

    posterior spoke-like cataracts
    SYMPTOMS

 and

    tortuosity of conjunctival vessels
    SYMPTOMS

 were found.

    His
    GENDER

    mother had the same ocular signs
    FAMILY

. The patient was also examined with

    fluorescein fundus angiography
    PARACLINICAL

.

The diagnostic value of the

    ocular abnormalities
    SYMPTOMS

 can be significant and are very indicative of the disease in

    hemizygous
    GENETICS

 and

    heterozygous
    GENETICS

 patients. Except the

    retinal vascular tortuosity
    SYMPTOMS

, we describe

    peripheric abnormalities of the retinal pigment epithelium
    SYMPTOMS

 suggesting another disease finding.

X linked disease
hemizygous
heterozygous


[Biochemical study of unusual cases of Fabry disease].

Fourteen members of family P. and four members of family N. were clinico-biochemically examined. Among twelve adult children (19-32 years old) of family P. five sons manifested angiokeratotic skin lesions and other clinical signs of Fabry disease. Three of the probands had additional symptoms not generally found in Fabry disease. Biochemical studies including an enzyme assay, analysis of storage products and alpha-galactosidase multiple forms, allowed us to confirm the diagnosis of Fabry disease in four affected brothers and to establish the heterozygous status of their mother. The data of biochemical investigation of patient N. with atypical variant of Fabry disease are also presented. The patient N. with strong skin lesions had a high residual alpha-galactosidase activity and unusual composition of alpha-galactosidase multiple forms.

Fourteen members of family P. and four members of family N. were

    clinico-biochemically examined
    PARACLINICAL

. Among twelve

    adult children (19-32 years old
    AGE

) of family P. five sons manifested

    angiokeratotic skin lesions
    SYMPTOMS

 and other

    clinical signs of Fabry disease
    SYMPTOMS

. Three of the probands had

    additional symptoms not generally found in Fabry disease
    SYMPTOMS

.

    Biochemical studies
    PARACLINICAL

 including an

    enzyme assay
    PARACLINICAL

,

    analysis of storage products and alpha-galactosidase multiple forms
    PARACLINICAL

, allowed us to confirm the diagnosis of

    Fabry disease
    DIAGNOSIS

 in

    four affected brothers
    FAMILY

 and to establish the

    heterozygous status of their mother
    FAMILY

. The data of

    biochemical investigation
    PARACLINICAL

 of patient N. with

    atypical variant of Fabry disease
    DIAGNOSIS

 are also presented. The patient N. with

    strong skin lesions
    SYMPTOMS

 had a

    high residual alpha-galactosidase activity
    BIOCHEMICAL

 and

    unusual composition of alpha-galactosidase multiple forms
    MICROSCOPIC

.

Fabry disease
atypical variant of Fabry disease


Retinal vein occlusion in a woman with heterozygous Fabry's disease.

Fabry's disease is associated with high incidence of thrombosis in hemizygous males and heterozygous females. We describe a woman with Fabry's disease who developed hemi-central retinal vein occlusion during the follow-up. The vein occlusion showed a fulminant course ending with a painful blind eye within a short period. Fabry's disease should be considered in the differential diagnosis of the vascular occlusive disorders especially in young patients.

    Fabry's disease
    DIAGNOSIS

 is associated with high incidence of

    thrombosis
    SYMPTOMS

 in

    hemizygous males
    GENETICS

 and

    heterozygous
    GENETICS

    females
    GENDER

. We describe a

    woman
    GENDER

 with

    Fabry's disease
    DIAGNOSIS

 who developed

    hemi-central retinal vein occlusion
    SYMPTOMS

 during the follow-up. The

    vein occlusion
    SYMPTOMS

 showed a

    fulminant course
    SYMPTOMS

 ending with a

    painful blind eye
    SYMPTOMS

 within a short period.

    Fabry's disease
    DIAGNOSIS

 should be considered in the

    differential diagnosis
    PARACLINICAL

 of the

    vascular occlusive disorders
    DIAGNOSIS

 especially in

    young
    AGE

 patients.

Fabry's disease
Fabry's disease
Fabry's disease
vascular occlusive disorders

thrombosis
hemi-central retinal vein occlusion
vein occlusion
fulminant course
painful blind eye


Hybridization of chromosome 18 alpha-satellite DNA probe to chromosome 22.

Fluorescence in situ hybridization (FISH) of uncultured chorionic villus diploid cells with a chromosome 18 alpha-satellite DNA probe (D18Z1) revealed a third small signal in addition to two large signals. FISH analysis of diploid metaphase cells from cultured chorionic villus cells and from maternal lymphocytes revealed that the third signal resulted from hybridization to the centromere of chromosome 22. This is the first report of a variant involving D18Z1 detected by FISH and of hybridization of alpha-satellite from a sub-metacentric chromosome to the centromere of an acrocentric chromosome. We propose that this inherited variant resulted from insertion of chromosome 18 specific alpha-satellite DNA sequences into the centromeric region of chromosome 22.

    Fluorescence in situ hybridization (FISH) of uncultured chorionic villus diploid cells
    PARACLINICAL

 with a

    chromosome 18 alpha-satellite DNA probe (D18Z1)
    PARACLINICAL

 revealed a

    third small signal in addition to two large signals
    SYMPTOMS

.

    FISH analysis of diploid metaphase cells from cultured chorionic villus cells and from maternal lymphocytes
    PARACLINICAL

 revealed that the third signal resulted from

    hybridization to the centromere of chromosome 22
    GENETICS

. This is the first report of a

    variant involving D18Z1
    GENETICS

 detected by

    FISH
    PARACLINICAL

 and of

    hybridization of alpha-satellite from a sub-metacentric chromosome to the centromere of an acrocentric chromosome
    MICROSCOPIC

. We propose that this

    inherited
    GENETICS

 variant resulted from

    insertion of chromosome 18 specific alpha-satellite DNA sequences into the centromeric region of chromosome 22
    GENETICS

.


Coexistence of Fabry's disease and systemic lupus erythematosus.

This report describes a case of a female with systemic lupus erythematosus, who was subsequently diagnosed with Fabry's disease. Due to similarities in the organs involved by these two multisystem disorders, difficulties were encountered in establishing a prompt diagnosis of Fabry's disease. That and subsequent management of this patient are discussed. A literature review of the coexistence of the two disorders along with the potential pathogenic mechanisms explaining this association are explored.

This report describes a case of a

    female
    GENDER

 with

    systemic lupus erythematosus
    DIAGNOSIS

, who was subsequently diagnosed with

    Fabry's disease
    DIAGNOSIS

. Due to

    similarities in the organs involved by these two multisystem disorders
    SYMPTOMS

, difficulties were encountered in establishing a prompt diagnosis of

    Fabry's disease
    DIAGNOSIS

. That and subsequent management of this patient are discussed. A literature review of the

    coexistence of the two disorders
    DIAGNOSIS

 along with the potential pathogenic mechanisms explaining this association are explored.

systemic lupus erythematosus
Fabry's disease
Fabry's disease
coexistence of the two disorders


Angiokeratoma corporis diffusum associated with galactosialidosis.

We describe a 34-year-old Japanese man with generalized angiokeratomas and various neurological symptoms since childhood. A number of reddish papules were scattered over his entire body and were especially numerous on his elbows, knees, penis and scrotum. An electron-microscopic study revealed a number of vacuoles in the cytoplasm of the vascular endothelial cells. This finding suggests that the angiokeratomas resulted from an injury of the endothelial cells due to the storage of metabolic material. A laboratory examination demonstrated a deficiency of both the beta-galactosidase and neuramidase activity in his leukocytes and fibroblasts. A restriction site analysis of PCR-amplified genomic DNA revealed that the patient had an mRNA splicing junction mutation at the 5' donor splice site of the exon 7/intron 7 junction in the protective protein gene.

We describe a

    34-year-old
    AGE

    Japanese
    ETHNICITY

    man
    GENDER

 with

    generalized angiokeratomas
    SYMPTOMS

 and

    various neurological symptoms
    SYMPTOMS

 since

    childhood
    AGE

. A

    number of reddish papules were scattered over his entire body and were especially numerous on his elbows, knees, penis and scrotum
    SYMPTOMS

. An

    electron-microscopic study
    PARACLINICAL

 revealed a

    number of vacuoles in the cytoplasm of the vascular endothelial cells
    MICROSCOPIC

. This finding suggests that the

    angiokeratomas
    SYMPTOMS

 resulted from an

    injury of the endothelial cells
    MICROSCOPIC

 due to the

    storage of metabolic material
    MICROSCOPIC

. A

    laboratory examination
    PARACLINICAL

 demonstrated a

    deficiency of both the beta-galactosidase and neuramidase activity in his leukocytes and fibroblasts
    BIOCHEMICAL

. A

    restriction site analysis of PCR-amplified genomic DNA
    PARACLINICAL

 revealed that the patient had an

    mRNA splicing junction mutation at the 5' donor splice site of the exon 7/intron 7 junction in the protective protein gene
    GENETICS

.


[Multiple Fordyce-type angiokeratomas of the scrotum. An iatrogenic case].

Angiokeratoma is a wart-like vascular lesion of the skin. There are five types of angiokeratoma: the Mibelli-type, the Fordyce-type, the solitary and multiple (papular) types, the angiokeratoma circumscriptum, and the angiokeratoma corporis diffusum. The "Mibelli-type" occurs on the acral sites, mainly digits, of young people affected by repeated attacks of chilblain, which result in a deleterious effects on vessel walls. The "Fordyce-type" occurs on the scrotal skin of young and adults as a secondary effect to an increased blood pressure in scrotal veins. An equivalent form affecting adult females and occurring analogously on the skin of the vulva is also on record. The "solitary and multiple papular types" of young individuals affect the lower extremities and is considered a consequence of a congenital deficiency of elastic tissue in regional veins. We suggest the term "acquired angiokeratomas" for these three above mentioned clinical forms of angiokeratomas, leaving apart the other two types which are essentially congenital. In fact the "angiokeratoma circumscriptum" is a nevoid hamartomatous lesion arising early in life during infancy or childhood, sometimes in association with other congenital malformation of other sites, while the "angiokeratoma corporis diffusum" almost always occurs in association with enzyme disorders, usually alpha-galactosidase A enzyme deficiency (Anderson-Fabry disease), an X-linked recessive disorder affecting homozigous male patients in their adulthood.

A case of multiple angiokeratomas of the scrotum (Fordyce-type) arisen in a 62-year old male patient following surgical amputation of the penis and bilateral inguino-crural lymphadenectomy for carcinoma of the penis is reported on.

Although they are well on record cases of angiokeratomas of the scrotum arising after surgical injuries to the outer vein pudenda (mainly following inguinocrural hernioplasty), based on a computerized search of the literature on theme this case represents the first iatrogenic example of such an occurrence. The pathogenetic mechanism leading to the the rise of angiokeratomas mediated by the increase of the blood pressure in the superficial scrotal veins is discussed. This example represents an additional case report of inevitable and sometimes unsuspected iatrogenic pathology in medicine.

    Angiokeratoma
    DIAGNOSIS

 is a

    wart-like vascular lesion of the skin
    SYMPTOMS

. There are five types of

    angiokeratoma
    DIAGNOSIS

: the

    Mibelli-type
    DIAGNOSIS

, the

    Fordyce-type
    DIAGNOSIS

, the

    solitary and multiple (papular) types
    SYMPTOMS

, the

    angiokeratoma circumscriptum
    DIAGNOSIS

, and the

    angiokeratoma corporis diffusum
    DIAGNOSIS

. The "

    Mibelli-type"
    DIAGNOSIS

 occurs

    on the acral sites, mainly digits
    SYMPTOMS

, of

    young
    AGE

 people affected by

    repeated attacks of chilblain
    SYMPTOMS

, which result in a

    deleterious effects on vessel walls
    SYMPTOMS

. The "

    Fordyce-type"
    SYMPTOMS

 occurs

    on the scrotal skin
    SYMPTOMS

 of

    young
    AGE

    and adults
    AGE

 as a secondary effect to an

    increased blood pressure in scrotal veins
    SYMPTOMS

. An equivalent form affecting

    adult
    AGE

    females
    GENDER

 and occurring analogously

    on the skin of the vulva
    SYMPTOMS

 is also on record. The "

    solitary and multiple papular types"
    SYMPTOMS

 of

    young
    AGE

 individuals

    affect the lower extremities
    SYMPTOMS

 and is considered a consequence of a

    congenital deficiency of elastic tissue in regional veins
    SYMPTOMS

. We suggest the term "

    acquired angiokeratomas
    SYMPTOMS

" for these three above mentioned clinical forms of

    angiokeratomas
    SYMPTOMS

, leaving apart the other two types which are essentially congenital. In fact the "

    angiokeratoma circumscriptum
    DIAGNOSIS

" is a

    nevoid hamartomatous lesion
    SYMPTOMS

 arising

    early in life during infancy or childhood
    AGE

, sometimes in

    association with other congenital malformation of other sites
    SYMPTOMS

, while the "

    angiokeratoma corporis diffusum
    DIAGNOSIS

" almost always occurs in association with

    enzyme disorders
    DIAGNOSIS

, usually

    alpha-galactosidase A enzyme deficiency (Anderson-Fabry disease)
    BIOCHEMICAL

, an

    X-linked recessive disorder
    GENETICS

 affecting

    homozigous
    GENETICS

    male
    GENDER

 patients

    in their adulthood
    AGE

.

A case of

    multiple angiokeratomas of the scrotum (Fordyce-type)
    SYMPTOMS

 arisen in a

    62-year old
    AGE

    male
    GENDER

 patient following

    surgical amputation of the penis
    MEDICATION

 and

    bilateral inguino-crural lymphadenectomy
    MEDICATION

 for

    carcinoma of the penis
    DIAGNOSIS

 is reported on.

Although they are well on record cases of

    angiokeratomas of the scrotum
    SYMPTOMS

 arising after

    surgical injuries to the outer vein pudenda
    SYMPTOMS

 (mainly following

    inguinocrural hernioplasty
    MEDICATION

), based on a computerized search of the literature on theme this case represents the first iatrogenic example of such an occurrence. The pathogenetic mechanism leading to the the rise of

    angiokeratomas
    SYMPTOMS

 mediated by the

    increase of the blood pressure in the superficial scrotal veins
    SYMPTOMS

 is discussed. This example represents an additional case report of inevitable and sometimes unsuspected iatrogenic pathology in medicine.

Angiokeratoma
angiokeratoma
Mibelli-type
Fordyce-type
angiokeratoma circumscriptum
angiokeratoma corporis diffusum
Mibelli-type"
angiokeratoma circumscriptum
angiokeratoma corporis diffusum
enzyme disorders
carcinoma of the penis


Angiokeratoma: a cause of scrotal bleeding.

We report a case of Fordyce angiokeratoma which presented with bleeding from the scrotum. The difference between Fordyce's angiokeratoma and Fabry's angiokeratoma corporis diffusum is described. The diagnosis, treatment and prognosis of scrotal angiokeratoma are discussed.

We report a case of

    Fordyce angiokeratoma
    DIAGNOSIS

 which presented with

    bleeding from the scrotum
    SYMPTOMS

. The difference between

    Fordyce's angiokeratoma
    DIAGNOSIS

 and

    Fabry's angiokeratoma corporis diffusum
    DIAGNOSIS

 is described. The diagnosis, treatment and prognosis of

    scrotal angiokeratoma
    DIAGNOSIS

 are discussed.

Fordyce angiokeratoma
Fordyce's angiokeratoma
Fabry's angiokeratoma corporis diffusum
scrotal angiokeratoma


Identification of a novel point mutation (S65T) in alpha-galactosidase A gene in Chinese patients with Fabry disease. Mutations in brief no. 169. Online.

Fabry disease is an X-linked inborn error of sphingolipid catabolism resulting from deficient enzyme activity of alpha-galactosidase A. The molecular defects of human alpha-galactosidase A gene causing Fabry disease have been characterized, including gene rearrangement and point mutations, which show the genetic heterogeneity in Fabry disease. To characterize the molecular defects of these patients, each exon of alpha-galactosidase A gene including intron-exon junctions were PCR amplified using biotin-labelled primer and sequenced using magnetic beads solid-phase sequencing. A G to C transversion was identified in the last nucleotide of exon 1 in two unrelated Chinese patients. This mutation obliterates an EcoN1 restriction site. Family studies show close linkage with the affected family members. Screening of 100 alleles (22 males, 39 females) of unrelated normal Chinese can not find this mutation. This mutation not only changes the amino acid from serine to threonine, but also likely cause splicing defects. To our knowledge, this is the first report of mutation in Chinese patients with Fabry disease, and a novel mutation causing Fabry disease not reported in literature previously.

    Fabry disease
    DIAGNOSIS

 is an

    X-linked
    GENETICS

    inborn error of sphingolipid catabolism
    DIAGNOSIS

 resulting from deficient enzyme activity of alpha-galactosidase A. The

    molecular defects
    GENETICS

 of

    human alpha-galactosidase A gene
    GENETICS

 causing

    Fabry disease
    DIAGNOSIS

 have been characterized, including

    gene rearrangement
    GENETICS

 and

    point mutations
    GENETICS

, which show the

    genetic heterogeneity
    GENETICS

 in

    Fabry disease
    DIAGNOSIS

. To characterize the molecular defects of these patients,

    each exon of alpha-galactosidase A gene including intron-exon junctions were PCR amplified using biotin-labelled primer
    PARACLINICAL

 and

    sequenced using magnetic beads solid-phase sequencing
    PARACLINICAL

.

    A G to C transversion was identified in the last nucleotide of exon 1
    GENETICS

 in two unrelated

    Chinese
    ETHNICITY

 patients. This

    mutation obliterates an EcoN1 restriction site
    GENETICS

.

    Family studies
    PARACLINICAL

 show

    close linkage with the affected family members
    FAMILY

. Screening of 100 alleles (22

    males
    GENDER

, 39

    females
    GENDER

) of unrelated normal

    Chinese
    ETHNICITY

 can not find this mutation. This mutation not only

    changes the amino acid from serine to threonine
    GENETICS

, but also likely cause

    splicing defects
    GENETICS

. To our knowledge, this is the first report of mutation in

    Chinese
    ETHNICITY

 patients with

    Fabry disease
    DIAGNOSIS

, and a novel mutation causing

    Fabry disease
    DIAGNOSIS

 not reported in literature previously.

Fabry disease
inborn error of sphingolipid catabolism
Fabry disease
Fabry disease
Fabry disease
Fabry disease


Fabry's disease--a case report and review of literatures reported in Korea.

Fabry's disease is a rare, X-linked disorder of the glycosphingolipid metabolism, in which a partial or total deficiency of a lysosomal alpha(alpha)-galactosidase results in the progressive accumulation of neutral glycosphingolipids with terminal alpha galactose moieties (i.e., cerebroside di- and trihexoside) in most body fluids and tissues. Accumulation of neutral glycosphingolipids occurs within the lysosomes of endothelial, perithelial, and smooth muscle cells of the myocardial and renal systems; to a lesser extent in reticuloendothelial and connective cells of the cornea; and in ganglion and perineural cells of the autonomic nervous system. In Korea, 7 cases of Fabry's disease have been reported. A 29-year-old man with fever and headache had typical skin findings and a family history of Fabry's disease, and it was confirmed through renal biopsy and enzyme assay for alpha-galactosidase. We report a case of Fabry's disease with a review of the literatures reported in Korea.

    Fabry's disease
    DIAGNOSIS

 is a

    rare, X-linked
    GENETICS

    disorder of the glycosphingolipid metabolism
    DIAGNOSIS

, in which a

    partial or total deficiency of a lysosomal alpha(alpha)-galactosidase
    BIOCHEMICAL

 results in the

    progressive accumulation of neutral glycosphingolipids with terminal alpha galactose moieties (i.e., cerebroside di- and trihexoside) in most body fluids and tissues
    MICROSCOPIC

.

    Accumulation of neutral glycosphingolipids occurs within the lysosomes of endothelial, perithelial, and smooth muscle cells of the myocardial and renal systems
    MICROSCOPIC

; to a lesser extent

    in reticuloendothelial and connective cells of the cornea; and in ganglion and perineural cells of the autonomic nervous system
    MICROSCOPIC

. In

    Korea
    ETHNICITY

, 7 cases of

    Fabry's disease
    DIAGNOSIS

 have been reported. A

    29-year-old
    AGE

    man
    GENDER

 with

    fever
    SYMPTOMS

 and

    headache
    SYMPTOMS

 had

    typical skin findings
    SYMPTOMS

 and a

    family history of Fabry's disease
    FAMILY

, and it was confirmed through

    renal biopsy
    PARACLINICAL

 and

    enzyme assay for alpha-galactosidase
    PARACLINICAL

. We report a case of

    Fabry's disease
    DIAGNOSIS

 with a review of the literatures reported in

    Korea
    ETHNICITY

.


Fabry's disease: a multidisciplinary disorder.

Fabry's disease is an X-linked hereditary disorder resulting in accumulation of a glycolipid (galactosylgalactosyl glucosylceramide) due to deficiency of alpha-galactosidase A. The diagnosis can be made by histopathologic examination of skin biopsy, low activity of alpha-galactosidase in leucocytes and genetic examination. Treatment is symptomatic. We want to stress the multidisciplinary collaboration necessary to deal with this condition, in order to prevent acceleration of symptoms.

    Fabry's disease
    DIAGNOSIS

 is an

    X-linked hereditary disorder
    GENETICS

 resulting in

    accumulation of a glycolipid (galactosylgalactosyl glucosylceramide)
    MICROSCOPIC

 due to deficiency of alpha-galactosidase A. The diagnosis can be made by

    histopathologic examination of skin biopsy
    PARACLINICAL

,

    low activity of alpha-galactosidase in leucocytes
    BIOCHEMICAL

 and

    genetic examination
    PARACLINICAL

. Treatment is

    symptomatic
    MEDICATION

. We want to stress the multidisciplinary collaboration necessary to deal with this condition, in order to prevent

    acceleration of symptoms
    SYMPTOMS

.


Cardiac transplantation for Fabry's disease.

Fabry's disease is a rare cause of cardiomyopathy. There are no previous reported cases of cardiac transplantation for end-stage cardiomyopathy secondary to Fabry's disease. Recurrence of disease in allografts following renal transplantation has been documented, but the course following heart transplantation is not known. A 53-year-old female presented with congestive heart failure and was found to have end-stage restrictive cardiomyopathy secondary to Fabry's disease, as diagnosed by endomyocardial biopsy. She underwent cardiac transplantation. Eight weeks post-transplantation, electron microscopy of an endomyocardial biopsy specimen showed concentric lamellar inclusions within myocytes similar to inclusions seen in the preoperative biopsy and the explanted heart. However, subsequent biopsies up to one year after heart transplantation did not show any such inclusions. There has been no clinical evidence of Fabry's cardiomyopathy. Heart transplantation is a viable option for end-stage Fabry's cardiomyopathy. However, long term follow-up is required to determine clinical outcome.

    Fabry's disease
    DIAGNOSIS

 is a rare cause of

    cardiomyopathy
    DIAGNOSIS

. There are no previous reported cases of

    cardiac transplantation
    MEDICATION

 for

    end-stage cardiomyopathy secondary to Fabry's disease
    DIAGNOSIS

.

    Recurrence of disease in allografts
    SYMPTOMS

 following

    renal transplantation
    MEDICATION

 has been documented, but the course following

    heart transplantation
    MEDICATION

 is not known. A

    53-year-old
    AGE

    female
    GENDER

 presented with

    congestive heart failure
    SYMPTOMS

 and was found to have

    end-stage restrictive cardiomyopathy
    DIAGNOSIS

 secondary to

    Fabry's disease
    DIAGNOSIS

, as diagnosed by

    endomyocardial biopsy
    PARACLINICAL

.

    She
    GENDER

 underwent

    cardiac transplantation
    MEDICATION

. Eight weeks post

    -transplantation
    MEDICATION

,

    electron microscopy of an endomyocardial biopsy specimen
    PARACLINICAL

 showed

    concentric lamellar inclusions within myocytes similar to inclusions seen in the preoperative biopsy and the explanted heart
    MICROSCOPIC

. However,

    subsequent biopsies
    PARACLINICAL

 up to one year after

    heart transplantation
    MEDICATION

    did not show any such inclusions
    NEG_FINDINGS

. There has been

    no clinical evidence of Fabry's cardiomyopathy
    NEG_FINDINGS

.

    Heart transplantation
    MEDICATION

 is a viable option for

    end-stage Fabry's cardiomyopathy
    DIAGNOSIS

. However, long term follow-up is required to determine clinical outcome.

cardiac transplantation
renal transplantation
heart transplantation
cardiac transplantation
-transplantation
heart transplantation
Heart transplantation

Recurrence of disease in allografts
congestive heart failure


Granulomatous cheilitis: a study of six cases.

Granulomatous cheilitis (GC) is a very rare disorder of unknown etiology. Clinically, GC is characterised by recurrent swelling of the labial tissues, which may be followed by a permanent enlargement. Histologically, the typical form of GC is characterised by the formation of scattered aggregates of non-caseating granulomas. GC is the most frequent sign of orofacial granulomatosis, a disorder under which also encompasses sarcoidosis, Crohn's disease, atypical tuberculosis, Anderson-Fabry disease, possibly some allergic reactions, and Melkersson-Rosenthal syndrome (MRS). Some consider GC as an oligosymptomatic or monosymptomatic form of MRS.

In this study we examined the clinical records of six patients presenting with GC which were examined and treated in the Department of Oral Medicine and Pathology of the Dental School of Aristotle University of Thessaloniki (Greece) during a 16-year period. In five of six patients a persistent swelling of the lower lip was recorded, one of whom also developed swelling in the upper lip. In one case the swelling was present in both lips and in another the GC was the only clinical finding, while in the other five cases it was accompanied by at least one other feature of MRS. In five cases, the histological picture revealed non-caseating granulomas.

The treatment with the intralesional infusion of corticosteroids in three cases and the oral administration of corticosteroids in two cases was successful. One of the patients refused to be treated. This patient also presented later with permanent swelling of the upper lip.

    Granulomatous cheilitis (GC)
    DIAGNOSIS

 is a very rare disorder of unknown etiology. Clinically,

    GC
    DIAGNOSIS

 is characterised by

    recurrent swelling of the labial tissues
    SYMPTOMS

, which may be followed by a

    permanent enlargement
    SYMPTOMS

. Histologically, the typical form of

    GC
    DIAGNOSIS

 is characterised by the

    formation of scattered aggregates of non-caseating granulomas
    MICROSCOPIC

.

    GC
    DIAGNOSIS

 is the most frequent sign of

    orofacial granulomatosis
    DIAGNOSIS

, a disorder under which also encompasses

    sarcoidosis
    DIAGNOSIS

,

    Crohn's disease
    DIAGNOSIS

,

    atypical tuberculosis
    DIAGNOSIS

,

    Anderson-Fabry disease
    DIAGNOSIS

, possibly some

    allergic reactions
    DIAGNOSIS

, and

    Melkersson-Rosenthal syndrome (MRS)
    DIAGNOSIS

. Some consider

    GC
    DIAGNOSIS

 as an

    oligosymptomatic
    DIAGNOSIS

 or

    monosymptomatic form of MRS
    DIAGNOSIS

.

In this study we examined the clinical records of six patients presenting with

    GC
    DIAGNOSIS

 which were examined and treated in the Department of

    Oral Medicine and Pathology
    PARACLINICAL

 of the Dental School of Aristotle University of Thessaloniki (

    Greece
    ETHNICITY

) during a 16-year period. In five of six patients a

    persistent swelling of the lower lip
    SYMPTOMS

 was recorded, one of whom also developed

    swelling in the upper lip
    SYMPTOMS

. In one case the

    swelling was present in both lips
    SYMPTOMS

 and in another the

    GC
    SYMPTOMS

 was the only clinical finding, while in the other five cases it was accompanied by at least one

    other feature of MRS
    SYMPTOMS

. In five cases, the

    histological picture
    PARACLINICAL

 revealed

    non-caseating granulomas
    MICROSCOPIC

.

The

    treatment with the intralesional infusion of corticosteroids
    MEDICATION

 in three cases and the

    oral administration of corticosteroids
    MEDICATION

 in two cases was successful. One of the patients

    refused to be treated
    NEG_FINDINGS

. This patient also presented later with

    permanent swelling of the upper lip
    SYMPTOMS

.

Granulomatous cheilitis (GC)
GC
GC
GC
orofacial granulomatosis
sarcoidosis
Crohn's disease
atypical tuberculosis
Anderson-Fabry disease
allergic reactions
Melkersson-Rosenthal syndrome (MRS)
GC
oligosymptomatic
monosymptomatic form of MRS
GC


Fabry's disease presenting as syncope, angiokeratomas, and spoke-like cataracts in a young man: discussion of the differential diagnosis.

A 44-year-old male with a remote history of skin lesions and cataracts presented with subacute onset of syncope. The presentation and the differential diagnosis in this case of Fabry's disease are discussed. The pathophysiology, diagnosis, clinical manifestations, and treatment of this disorder are discussed, with a review of the literature. Fludrocortisone acetate therapy resulted in a reduction in the patient's syncopal event frequency. Serum enzymatic assay and skin biopsy are useful in the diagnosis of Fabry's disease. We advocate a conservative approach to the oculocutaneous symptoms and suggest appropriate interventions for the renovascular and autonomic nervous system complications of this disorder.

A

    44-year-old
    AGE

    male
    GENDER

 with a

    remote history of skin lesions and cataracts
    SYMPTOMS

 presented with

    subacute onset of syncope
    SYMPTOMS

. The presentation and the

    differential diagnosis
    PARACLINICAL

 in this case of

    Fabry's disease
    DIAGNOSIS

 are discussed. The pathophysiology, diagnosis, clinical manifestations, and treatment of this disorder are discussed, with a review of the literature.

    Fludrocortisone acetate therapy
    MEDICATION

 resulted in a

    reduction in the patient's syncopal event frequency
    SYMPTOMS

.

    Serum enzymatic assay
    PARACLINICAL

 and

    skin biopsy
    PARACLINICAL

 are useful in the diagnosis of

    Fabry's disease
    DIAGNOSIS

. We advocate a

    conservative approach
    MEDICATION

 to the

    oculocutaneous symptoms
    SYMPTOMS

 and suggest appropriate interventions for the

    renovascular and autonomic nervous system complications
    SYMPTOMS

 of this disorder.

Fludrocortisone acetate therapy
conservative approach


Molecular interactions between Hb alpha-G Philadelphia, HbC, and HbS: phenotypic implications for SC alpha-G Philadelphia disease.

We show here that alpha2(G-Phila.) beta2(C) has an increased rate of crystal nucleation compared to alpha2 beta2(C) (HbC). We conclude from this finding that position alpha68, the mutation site of alpha2(G-Phila.) beta2 (HbG(Philadelphia)), is a contact site in the crystal of HbC. In addition, that HbS enhances HbC crystallization (additive to the effect of alpha(G-Phila.) as shown here) and that alpha(G-Phila.) inhibits polymerization of HbS are pathogenically relevant previously known facts. All of these findings help explain the phenotype of an individual simultaneously heterozygous for the betaS, betaC, and the alpha(G-Phila.) genes (SC alpha-G Philadelphia disease). This disease is characterized by a mild clinical course, abundant circulating intraerythrocytic crystals, and increased folded red cells. This phenotype seems to be the result of increased crystallization and decreased polymerization brought about by the opposite effects of the gene product of the alpha(G-Phila.) gene on the betaC and betaS gene products. Some of the intraerythrocytic crystals in this syndrome are unusually long and thin, resembling sugar canes, unlike those seen in SC disease. The mild clinical course associated with increased crystallization implies that, in SC disease, polymerization of HbS is pathogenically more important than the crystallization induced by betaC chains. The SC alpha-G Philadelphia disease is an example of multiple hemoglobin chain interactions (epistatic effect among globin genes) creating a unique phenotype.

We show here that

    alpha2(G-Phila.) beta2(C)
    GENETICS

 has an increased rate of crystal nucleation compared to alpha2 beta2(C) (HbC). We conclude from this finding that

    position alpha68, the mutation site of alpha2(G-Phila.) beta2 (HbG(Philadelphia)), is
    GENETICS

 a contact site in the crystal of HbC. In addition, that

    HbS enhances HbC crystallization
    BIOCHEMICAL

 (additive to the effect of

    alpha(G-Phila.)
    BIOCHEMICAL

 as shown here) and that

    alpha(G-Phila.) inhibits polymerization of HbS
    BIOCHEMICAL

 are pathogenically relevant previously known facts. All of these findings help explain the phenotype of an individual

    simultaneously heterozygous for the betaS, betaC, and the alpha(G-Phila.) genes
    GENETICS

 (

    SC alpha-G Philadelphia disease)
    DIAGNOSIS

. This disease is characterized by a

    mild clinical course
    SYMPTOMS

,

    abundant circulating intraerythrocytic crystals
    MICROSCOPIC

, and

    increased folded red cells
    MICROSCOPIC

. This phenotype seems to be the result of

    increased crystallization
    BIOCHEMICAL

 and

    decreased polymerization
    BIOCHEMICAL

 brought about by the

    opposite effects of the gene product of the alpha(G-Phila.) gene on the betaC and betaS gene products
    GENETICS

.

    Some of the intraerythrocytic crystals
    MICROSCOPIC

 in this syndrome

    are unusually long and thin, resembling sugar canes, unlike those seen in SC disease
    SYMPTOMS

. The

    mild clinical course
    SYMPTOMS

 associated with

    increased crystallization
    SYMPTOMS

 implies that, in

    SC disease
    DIAGNOSIS

,

    polymerization of HbS
    BIOCHEMICAL

 is pathogenically more important than the

    crystallization induced by betaC chains
    BIOCHEMICAL

. The

    SC alpha-G Philadelphia disease
    DIAGNOSIS

 is an example of

    multiple hemoglobin chain interactions (epistatic effect among globin genes
    GENETICS

) creating a unique phenotype.

SC alpha-G Philadelphia disease)
SC disease
SC alpha-G Philadelphia disease


The vascular dementia of Fabry's disease.

Fabry's disease, a rare X-linked disorder of glycosphingolipid metabolism, can present as an insidious dementia in middle or later life. This genetic disorder produces a deficiency of alpha-galactosidase A which results in the deposition of glycosphingolipids in blood vessel walls in the brain as well as in the kidney, heart, peripheral nerves, and other organs. Among the cerebrovascular manifestations of this disorder is a vascular dementia from involvement of multiple small penetrating blood vessels. Fabry's disease is a consideration in the workup of an otherwise unexplained vascular dementia, particularly in males less than 65 years of age.

    Fabry's disease
    DIAGNOSIS

, a

    rare X-linked
    GENETICS

    disorder of glycosphingolipid metabolism
    DIAGNOSIS

, can present as an

    insidious dementia
    SYMPTOMS

 in

    middle or later life
    AGE

. This

    genetic disorder
    GENETICS

 produces a

    deficiency of alpha-galactosidase A
    BIOCHEMICAL

 which results in the

    deposition of glycosphingolipids in blood vessel walls in the brain as well as in the kidney, heart, peripheral nerves, and other organs
    MICROSCOPIC

. Among the

    cerebrovascular manifestations
    SYMPTOMS

 of this disorder is a

    vascular dementia from involvement of multiple small penetrating blood vessels
    SYMPTOMS

.

    Fabry's disease
    DIAGNOSIS

 is a consideration in the workup of an otherwise unexplained

    vascular dementia
    SYMPTOMS

, particularly in

    males
    GENDER

    less than 65 years of age
    AGE

.


Cutaneous manifestations of fucosidosis.

Angiokeratoma corporis diffusum (ACD) is still often thought to be synonymous with Anderson-Fabry disease, a deficiency of alpha-galactosidase. It is important, however, to consider other possible enzyme deficiencies in patients with ACD. We report an 8-year-old boy with neurodevelopmental delay who was diagnosed as having fucosidosis following recognition of ACD in the dermatology department. Other cutaneous features in this patient included distal transverse purple nail bands, acrocyanosis and a naevus anaemicus. Histology and electron microscopy of skin papules was consistent with angiokeratoma. Skeletal survey demonstrated dysostosis multiplex. The diagnosis was confirmed by leucocyte oligosaccharide enzyme analysis. There are only three previous reports of fucosidosis in the U.K.

    Angiokeratoma corporis diffusum
    SYMPTOMS

    (ACD)
    DIAGNOSIS

 is still often thought to be synonymous with

    Anderson-Fabry disease
    DIAGNOSIS

, a

    deficiency of alpha-galactosidase
    BIOCHEMICAL

. It is important, however, to consider other possible

    enzyme deficiencies
    BIOCHEMICAL

 in patients with

    ACD
    DIAGNOSIS

. We report an

    8-year-old
    AGE

    boy
    GENDER

 with

    neurodevelopmental delay
    SYMPTOMS

 who was diagnosed as having

    fucosidosis
    DIAGNOSIS

 following recognition of

    ACD
    DIAGNOSIS

 in the dermatology department. Other cutaneous features in this patient included

    distal transverse purple nail bands
    SYMPTOMS

,

    acrocyanosis
    SYMPTOMS

 and a

    naevus anaemicus
    SYMPTOMS

.

    Histology and electron microscopy of skin papules
    PARACLINICAL

 was consistent with

    angiokeratoma
    MICROSCOPIC

.

    Skeletal survey
    PARACLINICAL

 demonstrated

    dysostosis multiplex
    DIAGNOSIS

. The diagnosis was confirmed by

    leucocyte oligosaccharide enzyme analysis
    PARACLINICAL

. There are only three previous reports of

    fucosidosis
    DIAGNOSIS

 in the U.K.

Angiokeratoma corporis diffusum
neurodevelopmental delay
distal transverse purple nail bands
acrocyanosis
naevus anaemicus

(ACD)
Anderson-Fabry disease
ACD
fucosidosis
ACD
dysostosis multiplex
fucosidosis

deficiency of alpha-galactosidase
enzyme deficiencies


[Complete atrioventricular block disclosing Fabry's disease].

Fabry's disease is a hereditary sex-linked sphinglopidosis characterised by abnormal cellular lipid overload in most organs due to deficiencies in enzymes implicated in the catabolism of certain neutral glycolipids. There are two main clinical forms; cardiovascular manifestations usually congestive cardiac failure, and renal manifestations progressing to renal failure and death due to uraemic coma. The authors report a case presenting with juvenile, symptomatic complete infrahisian atrioventricular block. They describe the different cardiovascular complications of Fabry's disease from a review of the medical literature.

    Fabry's disease
    DIAGNOSIS

 is a

    hereditary sex-linked
    GENETICS

    sphinglopidosis
    DIAGNOSIS

 characterised by

    abnormal cellular lipid overload in most organs
    MICROSCOPIC

 due to

    deficiencies in enzymes implicated in the catabolism of certain neutral glycolipids
    BIOCHEMICAL

. There are two main clinical forms;

    cardiovascular manifestations
    SYMPTOMS

 usually

    congestive cardiac failure
    SYMPTOMS

, and

    renal manifestations
    SYMPTOMS

 progressing to

    renal failure
    SYMPTOMS

 and

    death
    SYMPTOMS

 due to

    uraemic coma
    SYMPTOMS

. The authors report a case presenting with

    juvenile
    DIAGNOSIS

,

    symptomatic complete infrahisian atrioventricular block
    SYMPTOMS

. They describe the different

    cardiovascular complications
    SYMPTOMS

 of

    Fabry's disease
    DIAGNOSIS

 from a review of the medical literature.

Fabry's disease
sphinglopidosis
juvenile
Fabry's disease


Pulmonary involvement in Fabry disease.

Fabry disease is an X-linked inborn error of metabolism resulting from deficient activity of alpha-galactosidase A. Although several case reports have suggested an association between Fabry disease and airway obstruction, this has not been investigated in a large series of patients. We studied 25 unselected, consecutive, enzymatically diagnosed men referred to a General Clinical Research Center for evaluation. Thirty-six percent complained of dyspnea, and 24% had cough and/or wheezing. Symptoms were similar in smokers and nonsmokers. Nine (36%) had airway obstruction on spirometry; this finding was associated with age > or = 26 yr (p < 0.05) and dyspnea or wheezing (p < 0.005), but only weakly with smoking (p = 0.062). Five of eight patients responded to bronchodilators, but all 10 methacholine challenges were negative. Chest radiographs revealed normal lung fields in 24 patients and streaky bibasilar densities in one. No pulmonary uptake occurred on 67Ga citrate scans (18 patients) and 111In-tagged leukocyte scans (16 patients). Specific alpha-galactosidase A mutations were identified in 17 patients; all three patients with frameshift mutations and both subjects with the D264V missense mutation had obstructive impairment. We conclude that airway obstruction commonly occurs in patients with Fabry disease regardless of smoking history, and it increases with age. The presence of obstruction may be associated with certain mutations and most likely results from fixed narrowing of the airways by accumulated glycosphingolipid.

    Fabry disease
    DIAGNOSIS

 is an

    X-linked inborn error of metabolism
    GENETICS

 resulting from deficient activity of alpha-galactosidase A. Although several case reports have suggested an association between

    Fabry disease
    DIAGNOSIS

 and

    airway obstruction
    SYMPTOMS

, this has not been investigated in a large series of patients. We studied 25 unselected, consecutive, enzymatically diagnosed

    men
    GENDER

 referred to a General Clinical Research Center for evaluation. Thirty-six percent complained of

    dyspnea
    SYMPTOMS

, and 24% had

    cough and/or wheezing
    SYMPTOMS

. Symptoms were similar in smokers and

    nonsmokers
    GENDER

. Nine (36%) had

    airway obstruction
    SYMPTOMS

 on

    spirometry
    PARACLINICAL

; this finding was associated with

    age > or = 26 yr
    AGE

 (p < 0.05) and

    dyspnea or wheezing
    SYMPTOMS

 (p < 0.005), but only weakly with

    smoking
    MEDICATION

 (p = 0.062). Five of eight patients responded to

    bronchodilators
    MEDICATION

, but

    all 10 methacholine challenges were negative
    NEG_FINDINGS

.

    Chest radiographs
    PARACLINICAL

 revealed

    normal lung fields
    NEG_FINDINGS

 in 24 patients and

    streaky bibasilar densities
    SYMPTOMS

 in one.

    No pulmonary uptake occurred on 67Ga citrate scans
    NEG_FINDINGS

 (18 patients) and

    111In-tagged leukocyte scans
    PARACLINICAL

 (16 patients).

    Specific alpha-galactosidase A mutations
    GENETICS

 were identified in 17 patients; all three patients with

    frameshift mutations
    GENETICS

 and both subjects with the

    D264V missense mutation
    GENETICS

 had

    obstructive impairment
    SYMPTOMS

. We conclude that

    airway obstruction
    SYMPTOMS

 commonly occurs in patients with

    Fabry disease
    DIAGNOSIS

    regardless of smoking history
    NEG_FINDINGS

, and it increases with

    age
    AGE

. The presence of

    obstruction
    SYMPTOMS

 may be associated with certain mutations and most likely results from

    fixed narrowing of the airways
    SYMPTOMS

 by

    accumulated glycosphingolipid
    MICROSCOPIC

.

Fabry disease
Fabry disease
Fabry disease

airway obstruction
dyspnea
cough and/or wheezing
airway obstruction
dyspnea or wheezing
streaky bibasilar densities
obstructive impairment
airway obstruction
obstruction
fixed narrowing of the airways


Subclinical Fabry's disease occurring in the context of IgA nephropathy.

A 28-year-old male patient with both IgA nephropathy and an unusual case of Fabry's disease has been followed for 10 years. Diagnosis of both these diseases was made by histological examination of renal biopsy tissues and the enzyme activities of alpha-galactosidase A. Serial biopsies revealed the hithertofore unrecognized process of glomerular glycolipid accumulation peculiar to Fabry's disease at the initial stages of the disease. Physical examinations and routine laboratory analyses failed to show significant signs of Fabry's disease throughout the 10-year period. While alpha-galactosidase A activity is markedly decreased in the plasma of this patient as in classical Fabry hemizygotes, the activity in leukocytes and culture fibroblasts showed a considerable residual activity. Fabry's disease associated with IgA nephropathy apparently is extremely rare, and the present subclinical case is unique in that the early stages of substrate accumulation are demonstrable.

A

    28-year-old
    AGE

    male
    GENDER

 patient with

    both IgA nephropathy
    DIAGNOSIS

 and an

    unusual case of Fabry's disease
    DIAGNOSIS

 has been followed for 10 years. Diagnosis of both these diseases was made by

    histological examination of renal biopsy tissues
    PARACLINICAL

 and the enzyme activities of alpha-galactosidase A.

    Serial biopsies
    PARACLINICAL

 revealed the hithertofore unrecognized

    process of glomerular glycolipid accumulation peculiar to Fabry's disease
    MICROSCOPIC

 at the initial stages of the disease.

    Physical examinations and routine laboratory analyses
    NEG_FINDINGS

    failed to show significant signs of Fabry's disease throughout the 10-year period
    NEG_FINDINGS

. While

    alpha-galactosidase A activity is markedly decreased in the plasma
    BIOCHEMICAL

 of this patient as in

    classical Fabry hemizygotes
    FAMILY

,

    the activity in leukocytes and culture fibroblasts showed a considerable residual activity
    BIOCHEMICAL

.

    Fabry's disease associated with IgA nephropathy
    DIAGNOSIS

 apparently is extremely rare, and the present subclinical case is unique in that the

    early stages of substrate accumulation
    MICROSCOPIC

 are demonstrable.


A characteristic dissection microscopy appearance of a renal biopsy of a Fabry heterozygote.

We report a 15-year-old Fabry heterozygote presenting to us with asymptomatic proteinuria. During the dissection-microscopic examination, the glomeruli exhibited a characteristic swollen, glistening and white appearance. They were swollen and bulged out from the surface of the renal core. The glomerular tufts appeared to be filled with opaque and whitish material giving them a pale white discoloration. This appearance is due to the accumulation of glycosphingolipids in visceral epithelial cells of the kidney. This feature is important for the investigation of female patients with asymptomatic proteinuria, as in two thirds of Fabry heterozygotes the characteristic skin lesions are absent, and thus heterozygous Fabry disease may not be considered. We suggest that this easily demonstrable appearance can be the first evidence for the disease and pathologists should be aware of it in future.

We report a

    15-year-old
    AGE

    Fabry heterozygote
    DIAGNOSIS

 presenting to us with

    asymptomatic proteinuria
    BIOCHEMICAL

. During the

    dissection-microscopic examination
    PARACLINICAL

,

    the glomeruli
    MICROSCOPIC

 exhibited a

    characteristic swollen, glistening and white appearance
    SYMPTOMS

.

    They were swollen and bulged out from the surface of the renal core
    MICROSCOPIC

.

    The glomerular tufts appeared to be filled with opaque and whitish material
    MICROSCOPIC

 giving them a

    pale white discoloration
    SYMPTOMS

. This appearance is due to the

    accumulation of glycosphingolipids in visceral epithelial cells of the kidney
    MICROSCOPIC

. This feature is important for the investigation of

    female
    GENDER

 patients with

    asymptomatic proteinuria
    BIOCHEMICAL

, as in two thirds of

    Fabry heterozygotes
    DIAGNOSIS

 the

    characteristic skin lesions are absent
    NEG_FINDINGS

, and thus

    heterozygous
    GENETICS

    Fabry disease
    DIAGNOSIS

 may not be considered. We suggest that this easily demonstrable appearance can be the first evidence for the disease and pathologists should be aware of it in future.

Fabry heterozygote
Fabry heterozygotes
Fabry disease

asymptomatic proteinuria
asymptomatic proteinuria


High-flow priapism associated with Fabry's disease in a child: a case report and review of the literature.

We report a case of priapism in an 11-year-old boy known to have Fabry's disease. High flow was confirmed by color flow Doppler ultrasound and intracorporal blood gas measurements. Successful treatment was achieved by unilateral percutaneous Gelfoam embolization of the left internal pudendal artery. Previously reported cases of priapism associated with Fabry's disease were identified through a MEDLINE search of the English literature and review of the publications. Five reported cases of priapism associated with Fabry's disease were found, including those of 3 children. A report of a child with high-flow priapism that did not respond to conventional treatment including cavernovenous shunting was noted. Priapsim associated with Fabry's disease may be caused by unregulated high arterial inflow. Early recognition of the underlying pathophysiology may identify those cases that would be amenable to percutaneous embolization therapy and may obviate the need to pursue other ineffective conventional treatments.

We report a case of

    priapism
    SYMPTOMS

 in an

    11-year-old
    AGE

    boy
    GENDER

 known to have

    Fabry's disease
    DIAGNOSIS

.

    High flow
    SYMPTOMS

 was confirmed by

    color flow Doppler ultrasound
    PARACLINICAL

 and

    intracorporal blood gas measurements
    PARACLINICAL

. Successful treatment was achieved by

    unilateral percutaneous Gelfoam embolization of the left internal pudendal artery
    MEDICATION

. Previously reported cases of

    priapism
    SYMPTOMS

    associated with Fabry's disease
    DIAGNOSIS

 were identified through a MEDLINE search of the English literature and review of the publications. Five reported cases of

    priapism
    SYMPTOMS

    associated with Fabry's disease
    DIAGNOSIS

 were found, including those of 3

    children
    AGE

. A report of a

    child
    AGE

 with

    high-flow priapism
    SYMPTOMS

 that

    did not respond to conventional treatment including cavernovenous shunting
    NEG_FINDINGS

 was noted.

    Priapsim
    SYMPTOMS

    associated with Fabry's disease
    DIAGNOSIS

 may be caused by

    unregulated high arterial inflow
    SYMPTOMS

. Early recognition of the underlying pathophysiology may identify those cases that would be amenable to

    percutaneous embolization therapy
    MEDICATION

 and may obviate the need to

    pursue other ineffective conventional treatments
    NEG_FINDINGS

.

priapism
High flow
priapism
priapism
high-flow priapism
Priapsim
unregulated high arterial inflow

Fabry's disease
associated with Fabry's disease
associated with Fabry's disease
associated with Fabry's disease


[Angiokeratoma corporis diffusum universale (Fabry disease)].

Fabry's disease (Angiokeratoma corporis diffusum) is a rare X-chromosome linked recessive disorder belonging to the group of sphingolipoidoses. The basic defect involves the gene encoding alpha-galactosidase. Because this enzyme is responsible for decomposition of glycosphingolipids, its deficiency results in their accumulation in endothelial and smooth muscle cells. With time, generalized angiokeratomas, paresthesias, renal and cardiac insufficiency and cerebrovascular complications develop. We report a patient who in addition to the well-described findings also showed unique nail fold capillary changes not described so far. Analysis of serum concentration of alpha-galactosidase identified three female heterozygous carriers in the patient's family.

    Fabry's disease
    DIAGNOSIS

 (

    Angiokeratoma corporis diffusum
    SYMPTOMS

    )
    DIAGNOSIS

 is a

    rare X-chromosome linked recessive disorder
    GENETICS

 belonging to the group of

    sphingolipoidoses
    DIAGNOSIS

. The basic defect involves the

    gene encoding alpha-galactosidase
    GENETICS

. Because this enzyme is responsible for

    decomposition of glycosphingolipids
    BIOCHEMICAL

, its

    deficiency
    BIOCHEMICAL

 results in

    their accumulation in endothelial and smooth muscle cells
    MICROSCOPIC

. With time,

    generalized angiokeratomas
    SYMPTOMS

,

    paresthesias
    SYMPTOMS

,

    renal and cardiac insufficiency
    SYMPTOMS

 and

    cerebrovascular complications
    SYMPTOMS

 develop. We report a patient who in addition to the well-described findings also showed

    unique nail fold capillary changes
    SYMPTOMS

 not described so far.

    Analysis of serum concentration of alpha-galactosidase
    PARACLINICAL

 identified

    three female heterozygous carriers in the patient's family
    FAMILY

.

Angiokeratoma corporis diffusum
generalized angiokeratomas
paresthesias
renal and cardiac insufficiency
cerebrovascular complications
unique nail fold capillary changes

decomposition of glycosphingolipids
deficiency


Angiokeratoma corporis diffusum associated with beta-mannosidase deficiency.

Angiokeratoma corporis diffusum (ACD) was at one time thought to be synonymous with Anderson-Fabry disease. However, it is well known that widespread angiokeratomas may also be found in other lysosomal enzyme disorders, as well as in patients with normal enzyme activities. beta-Mannosidase deficiency was first described in humans in 1986; since then, only 11 cases of beta-mannosidase deficiency, which occurred in 8 families, have been reported. Although the clinical manifestations are varied, mental retardation and neurologic disorders are present in practically all patients.

We describe a 22-year-old woman who, since the age of 12 years, presented with progressive ACD affecting the lower limbs and the buttocks. Enzymatic studies revealed beta-mannosidase deficiency in cultured fibroblasts and in samples of serum and leukocytes. The patients's parents in turn exhibited intermediate enzyme levels, thus confirming the recessive autosomal hereditary nature of the disease. With the exception of an introverted character, the patient demonstrated no other anomalies.

This is the first case of beta-mannosidase deficiency diagnosed as a result of purely dermatologic findings, in the form of ACD. beta-Mannosidase deficiency should therefore be included when screening for enzyme abnormalities in patients with ACD, even in the absence of neurologic disorders or mental retardation.

    Angiokeratoma corporis diffusum (ACD)
    SYMPTOMS

 was at one time thought to be synonymous with

    Anderson-Fabry disease
    DIAGNOSIS

. However, it is well known that

    widespread angiokeratomas
    SYMPTOMS

 may also be found in other

    lysosomal enzyme disorders
    DIAGNOSIS

, as well as in patients with

    normal enzyme activities
    NEG_FINDINGS

.

    beta-Mannosidase deficiency
    BIOCHEMICAL

 was first described in humans in 1986; since then, only 11 cases of

    beta-mannosidase deficiency
    BIOCHEMICAL

, which occurred in 8 families, have been reported. Although the clinical manifestations are varied,

    mental retardation
    SYMPTOMS

 and

    neurologic disorders
    SYMPTOMS

 are present in practically all patients.

We describe a

    22-year-old
    AGE

    woman
    GENDER

 who,

    since the age of 12 years
    AGE

, presented with

    progressive ACD affecting the lower limbs and the buttocks
    SYMPTOMS

.

    Enzymatic studies
    PARACLINICAL

 revealed

    beta-mannosidase deficiency in cultured fibroblasts
    BIOCHEMICAL

    and in samples of serum and leukocytes
    BIOCHEMICAL

.

    The patients's parents in turn exhibited intermediate enzyme levels
    FAMILY

, thus confirming the

    recessive autosomal hereditary nature of the disease
    GENETICS

. With the exception of an

    introverted character
    FAMILY

, the patient demonstrated

    no other anomalies
    NEG_FINDINGS

.

This is the first case of

    beta-mannosidase deficiency
    BIOCHEMICAL

 diagnosed as a result of

    purely dermatologic findings
    SYMPTOMS

, in the form of

    ACD
    DIAGNOSIS

.

    beta-Mannosidase deficiency
    BIOCHEMICAL

 should therefore be included when screening for

    enzyme abnormalities
    BIOCHEMICAL

 in patients with

    ACD
    DIAGNOSIS

, even in the

    absence of neurologic disorders or mental retardation
    NEG_FINDINGS

.

Anderson-Fabry disease
lysosomal enzyme disorders
ACD
ACD


Uneven X inactivation in a female monozygotic twin pair with Fabry disease and discordant expression of a novel mutation in the alpha-galactosidase A gene.

We describe two female monozygotic (MZ) twins heterozygous for Fabry disease, an X linked disorder resulting from the deficient activity of alpha-galactosidase A. While one of the twins was clinically affected, the other was asymptomatic. Enzymatic assay of alpha-galactosidase in blood leucocytes, skin fibroblasts, Epstein-Barr virus transformed lymphoid cell lines, and hair follicles of the twins and their parents confirmed the heterozygous status of the twins and indicated that Fabry disease had occurred as a result of a de novo mutation. The son of the unaffected twin sister was shown to be hemizygous. Molecular analysis of the alpha-galactosidase A gene permitted the identification of an as yet undescribed point mutation at position 10182 of exon 5 which causes an Asp to Asn substitution at codon 231. Single strand conformation polymorphism (SSCP) analysis again showed the heterozygous status of the twins and a normal pattern in their parents. The basis for the discordant expression of this d novo mutation in the twins was investigated by studying their X inactivation status. Analysis of the inactive X specific methylation at the androgen receptor gene showed unbalanced inactivation in the twins' fibroblasts and in opposite directions. While the maternally derived X chromosome was preferentially active in the asymptomatic twin, the paternal X chromosome was active in the other, affected twin and was found in her hemizygotic nephew. These data suggest that the paternal X chromosome carries the de novo alpha-galactosidase A mutation and that uneven X inactivation is the underlying mechanism for disease expression in this novel female MZ twin pair. This is the first documented case of female twins discordant for Fabry disease.

We describe two

    female
    GENDER

    monozygotic (MZ) twins heterozygous for Fabry disease
    FAMILY

, an

    X linked disorder
    GENETICS

 resulting from the deficient activity of alpha-galactosidase A. While one of the twins was clinically affected, the other was

    asymptomatic
    NEG_FINDINGS

.

    Enzymatic assay of alpha-galactosidase in blood leucocytes, skin fibroblasts, Epstein-Barr virus transformed lymphoid cell lines, and hair follicles
    PARACLINICAL

 of the twins and their parents confirmed

    the heterozygous status of the twins
    FAMILY

 and indicated that

    Fabry disease
    DIAGNOSIS

 had occurred as a result of a

    de novo mutation
    GENETICS

.

    The son of the unaffected twin sister was shown to be hemizygous
    FAMILY

.

    Molecular analysis of the alpha-galactosidase A gene
    PARACLINICAL

 permitted the identification of an

    as yet undescribed point mutation at position 10182 of exon 5 which causes an Asp to Asn substitution at codon 231
    GENETICS

.

    Single strand conformation polymorphism (SSCP) analysis
    PARACLINICAL

 again showed

    the heterozygous status of the twins and a normal pattern in their parents
    FAMILY

. The basis for the

    discordant expression of this d novo mutation in the twins
    FAMILY

 was investigated by studying their

    X inactivation status
    GENETICS

.

    Analysis of the inactive X specific methylation at the androgen receptor gene
    PARACLINICAL

 showed

    unbalanced inactivation in the twins' fibroblasts and in opposite directions
    GENETICS

.

    While the maternally derived X chromosome was preferentially active in the asymptomatic twin, the paternal X chromosome was active in the other, affected twin and was found in her hemizygotic nephew
    GENETICS

. These data suggest that

    the paternal X chromosome carries the de novo alpha-galactosidase A mutation
    GENETICS

 and that

    uneven X inactivation
    GENETICS

 is the underlying mechanism for disease expression in this novel

    female
    GENDER

    MZ twin pair
    FAMILY

. This is the first documented case of

    female
    GENDER

    twins discordant for Fabry disease
    FAMILY

.


Immunofluorescence analysis of trihexosylceramide accumulated in the hearts of variant hemizygotes and heterozygotes with Fabry disease.

An immunofluorescence method was applied to detect trihexosylceramide accumulated in the cardiac tissues from a variant hemizygote and a heterozygous female with Fabry disease, the incidence of which had been suspected to be high.

An

    immunofluorescence method
    PARACLINICAL

 was applied to detect

    trihexosylceramide accumulated in the cardiac tissues
    MICROSCOPIC

 from a

    variant hemizygote
    GENETICS

 and a

    heterozygous
    GENETICS

    female
    GENDER

 with

    Fabry disease
    DIAGNOSIS

, the incidence of which had been suspected to be high.


Cerebrovascular complications of Fabry's disease.

Fabry's disease (FD) is a rare, sex-linked disorder resulting from alpha-galactosidase deficiency. Cerebrovascular complications have been reported in the literature but have not been systematically analyzed. We report 2 patients and review 51 previously reported cases (descriptive meta-analysis) to clarify the clinical, radiologic, and pathologic features. The average age at onset of cerebrovascular symptoms was 33.8 years for hemizygous individuals (n = 43) and 40.3 years of heterozygotes (n = 10). The most frequent symptoms and signs were as follows (in descending order of frequency): hemiparesis, vertigo/dizziness, diplopia, dysarthria, nystagmus, nausea/vomiting, head pain, hemiataxia, and ataxia of gait, in the hemizygote group; and memory loss, dizziness, ataxia, hemiparesis, loss of consciousness and hemisensory symptoms, in the heterozygote group. The vertebrobasilar circulation was symptomatic in 67% of the hemizygotes and 60% of the heterozygotes. Intracerebral hemorrhage was found in 4 patients (3 hemizygotes and 1 heterozygote). Elongated, ectatic, tortuous vertebral and basilar arteries were the most common angiographic and pathologic features. For the hemizygotes, the recurrence rate for cerebrovascular disease was 76% and the death rate was 55%; 86% of the heterozygotes had recurrent cerebrovascular event(s) and 40% died. The cerebrovascular manifestations of FD, in both hemizygotes and heterozygotes, are predominantly due to dilative arteriopathy of the vertebrobasilar circulation, frequently recur, and portend a poor prognosis.

    Fabry's disease (FD)
    DIAGNOSIS

 is a rare,

    sex-linked disorder
    GENETICS

 resulting from

    alpha-galactosidase deficiency
    BIOCHEMICAL

.

    Cerebrovascular complications
    SYMPTOMS

 have been reported in the literature but have not been systematically analyzed. We report 2 patients and review 51 previously reported cases (descriptive meta-analysis) to clarify the clinical, radiologic, and pathologic features. The average

    age at
    AGE

 onset of

    cerebrovascular symptoms
    SYMPTOMS

    was 33.8 years
    AGE

 for

    hemizygous individuals
    GENETICS

 (n = 43) and

    40.3 years
    AGE

 of

    heterozygotes
    GENETICS

 (n = 10). The most frequent symptoms and signs were as follows (in descending order of frequency):

    hemiparesis
    SYMPTOMS

,

    vertigo/dizziness
    SYMPTOMS

,

    diplopia
    SYMPTOMS

,

    dysarthria
    SYMPTOMS

,

    nystagmus
    SYMPTOMS

,

    nausea/vomiting
    SYMPTOMS

,

    head pain
    SYMPTOMS

,

    hemiataxia
    SYMPTOMS

, and

    ataxia of gait
    SYMPTOMS

, in the

    hemizygote
    GENETICS

 group; and

    memory loss
    SYMPTOMS

,

    dizziness
    SYMPTOMS

,

    ataxia
    SYMPTOMS

,

    hemiparesis
    SYMPTOMS

,

    loss of consciousness
    SYMPTOMS

 and

    hemisensory symptoms
    SYMPTOMS

, in the

    heterozygote
    GENETICS

 group.

    The vertebrobasilar circulation was symptomatic
    SYMPTOMS

 in 67% of the

    hemizygotes
    GENETICS

 and 60% of the

    heterozygotes
    GENETICS

.

    Intracerebral hemorrhage
    SYMPTOMS

 was found in 4 patients (3

    hemizygotes
    GENETICS

 and 1

    heterozygote
    GENETICS

).

    Elongated, ectatic, tortuous vertebral and basilar arteries
    SYMPTOMS

 were the most common angiographic and pathologic features. For the

    hemizygotes
    GENETICS

, the recurrence rate for

    cerebrovascular disease
    SYMPTOMS

 was 76% and the

    death
    SYMPTOMS

 rate was 55%; 86% of the

    heterozygotes
    GENETICS

 had

    recurrent cerebrovascular event(s)
    SYMPTOMS

 and 40%

    died
    SYMPTOMS

. The

    cerebrovascular manifestations
    SYMPTOMS

 of

    FD
    DIAGNOSIS

, in both

    hemizygotes
    GENETICS

 and

    heterozygotes
    GENETICS

, are predominantly due to

    dilative arteriopathy of the vertebrobasilar circulation
    SYMPTOMS

, frequently recur, and portend a poor prognosis.

sex-linked disorder
hemizygous individuals
heterozygotes
hemizygote
heterozygote
hemizygotes
heterozygotes
hemizygotes
heterozygote
hemizygotes
heterozygotes
hemizygotes
heterozygotes


Coexistence of gene mutations causing Fabry disease and Duchenne muscular dystrophy in a Japanese boy.

Both Fabry disease and Duchenne muscular dystrophy were confirmed by gene analysis in a Japanese boy. He developed muscle weakness at 4 years of age. A muscle biopsy revealed lamellar inclusion bodies in vascular endothelial cells in addition to myopathic changes with negative dystrophin staining. The myopathic symptoms progressed, and he died of pneumonia at 24 years of age. No clinical manifestations of Fabry disease were observed except for hypohidrosis and angiokeratoma. However, glycolipid accumulation was found in biopsied renal tissue. Molecular analysis demonstrated two gene mutations; a novel single-base deletion in exon 3 of the alpha-galactosidase gene, and a dystrophin gene deletion extending from exon 46 to exon 50. His mother was confirmed to be heterozygous for both gene deletions.

Both

    Fabry disease
    DIAGNOSIS

 and

    Duchenne muscular dystrophy
    DIAGNOSIS

 were confirmed by

    gene analysis
    PARACLINICAL

 in a

    Japanese
    ETHNICITY

    boy
    GENDER

.

    He
    GENDER

 developed

    muscle weakness
    SYMPTOMS

 at

    4 years of age
    AGE

. A

    muscle biopsy
    PARACLINICAL

 revealed

    lamellar inclusion bodies in vascular endothelial cells
    MICROSCOPIC

 in addition to

    myopathic changes
    MICROSCOPIC

 with

    negative dystrophin staining
    NEG_FINDINGS

. The

    myopathic symptoms
    SYMPTOMS

 progressed, and

    he
    GENDER

    died
    SYMPTOMS

 of

    pneumonia
    DIAGNOSIS

 at

    24 years of age
    AGE

.

    No clinical manifestations of Fabry disease were observed
    NEG_FINDINGS

 except for

    hypohidrosis
    SYMPTOMS

 and

    angiokeratoma
    SYMPTOMS

. However,

    glycolipid accumulation was found in biopsied renal tissue
    MICROSCOPIC

.

    Molecular analysis
    PARACLINICAL

 demonstrated

    two gene mutations; a novel single-base deletion in exon 3 of the alpha-galactosidase gene, and a dystrophin gene deletion extending from exon 46 to exon 50
    GENETICS

.

    His
    GENDER

    mother was confirmed to be heterozygous for both gene deletions
    FAMILY

.

Fabry disease
Duchenne muscular dystrophy
pneumonia

muscle weakness
myopathic symptoms
died
hypohidrosis
angiokeratoma