Simultaneous multicystic kidney and Anderson-Fabry disease: 2 separate entities or same side of the coin.

We present the case of a 54-year-old man with multicystic kidney and concomitant Anderson-Fabry disease. He was referred to our hospital with multiple renal and hepatic cysts, without apparent family history of autosomal dominant polycystic kidney disease. His clinical history suggested Anderson-Fabry disease, so an extensive work-up for Anderson-Fabry disease was subsequently undertaken. The alpha-galactosidase activity in his serum was low, and a final diagnosis of Anderson-Fabry disease with concomitant multicystic kidney was confirmed by genetic analysis.

We present the case of a

    54-year-old
    AGE

    man
    GENDER

 with

    multicystic kidney
    SYMPTOMS

 and

    concomitant Anderson-Fabry disease
    DIAGNOSIS

.

    He
    GENDER

 was referred to our hospital with

    multiple renal and hepatic cysts
    SYMPTOMS

,

    without apparent family history of autosomal dominant polycystic kidney disease
    NEG_FINDINGS

.

    His
    GENDER

 clinical history suggested

    Anderson-Fabry disease
    DIAGNOSIS

, so an extensive

    work-up
    PARACLINICAL

 for

    Anderson-Fabry disease
    DIAGNOSIS

 was subsequently undertaken. The

    alpha-galactosidase activity in his serum was low
    BIOCHEMICAL

, and a final diagnosis of

    Anderson-Fabry disease with concomitant multicystic kidney
    DIAGNOSIS

 was confirmed by

    genetic analysis
    PARACLINICAL

.

multicystic kidney
multiple renal and hepatic cysts


Interdisciplinary approach towards female patients with Fabry disease.

Fabry disease (FD) is a rare X-linked lysosomal storage disorder leading to an accumulation of globotriaosylceramides in the lysosomes of various organs.

Being X-chromosomal-linked, most studies in the past have focused on involvement in male patients. However, it has been elucidated recently that female patients can present typical organ involvement and thus need to be treated, respectively.

This review wants to give a systematical overview of the typical organ involvement in female patients with FD. Moreover, therapy recommendations especially for female patients are discussed.

    Fabry disease (FD)
    DIAGNOSIS

 is a

    rare X-linked
    GENETICS

    lysosomal storage disorder
    DIAGNOSIS

 leading to an

    accumulation of globotriaosylceramides in the lysosomes of various organs
    MICROSCOPIC

.

Being

    X-chromosomal-linked
    GENETICS

, most studies in the past have focused on involvement in

    male
    GENDER

 patients. However, it has been elucidated recently that

    female
    GENDER

 patients can present

    typical organ involvement
    SYMPTOMS

 and thus need to be treated, respectively.

This review wants to give a systematical overview of the typical

    organ involvement
    SYMPTOMS

 in

    female
    GENDER

 patients with

    FD
    DIAGNOSIS

. Moreover, therapy recommendations especially for

    female
    GENDER

 patients are discussed.

Fabry disease (FD)
lysosomal storage disorder
FD

typical organ involvement
organ involvement


[Stroke and cornea verticillata revealing Fabry's disease in a female].

Fabry's disease is a X-linked lysosomal storage disorder caused by an alpha-galactosidase A deficiency responsible for the accumulation of glycosphingolipids. Males are more severely and frequently affected than females. We report the case of a female who presented a stroke revealing Fabry's disease.

An 53-year-old woman, with cardiovascular risk factors and two previous transient ischemic attacks, was admitted with a brutal right hemiparisia. Cerebral MRI showed multiple white matter lesions in the cerebral hemispheres with multiple lacunar infarcts and ectatic vessels, cardiac echography revealed a hypertrophic concentric cardiomyopathy, and slit-lamp examination demonstrated a cornea verticillata. The sequencing of the alpha-galactosidase gene (GLA) revealed the c.150_151del mutation responsible for a loss of function.

As in the present case, ophthalmological examination is very useful to determine Fabry's disease as a cause of young onset stroke. Females may be affected by X-linked disease, as the Fabry's disease. Fabry's disease among females is mainly characterized by the involvement of the nervous and cardiovascular systems. The specific treatment is based on an enzyme replacement therapy by recombinant enzyme with cardiovascular benefit. Despite the presence of cardiovascular risk factors, this case demonstrates the importance of thorough standardized investigations including ophthalmological examination of young patients with stroke.

    Fabry's disease
    DIAGNOSIS

 is a

    X-linked
    GENETICS

    lysosomal storage disorder
    DIAGNOSIS

 caused by an

    alpha-galactosidase A deficiency
    BIOCHEMICAL

 responsible for the

    accumulation of glycosphingolipids
    MICROSCOPIC

.

    Males
    GENDER

 are more severely and frequently affected than

    females
    GENDER

. We report the case of a

    female
    GENDER

 who presented a

    stroke
    SYMPTOMS

 revealing

    Fabry's disease
    DIAGNOSIS

.

An

    53-year-old
    AGE

    woman
    GENDER

, with

    cardiovascular risk factors
    SYMPTOMS

 and

    two previous transient ischemic attacks
    SYMPTOMS

, was admitted with a

    brutal right hemiparisia
    SYMPTOMS

.

    Cerebral MRI
    PARACLINICAL

 showed

    multiple white matter lesions in the cerebral hemispheres with multiple lacunar infarcts and ectatic vessels
    SYMPTOMS

,

    cardiac echography
    PARACLINICAL

 revealed a

    hypertrophic concentric cardiomyopathy
    DIAGNOSIS

, and

    slit-lamp examination
    PARACLINICAL

 demonstrated a

    cornea verticillata
    SYMPTOMS

. The

    sequencing of the alpha-galactosidase gene (GLA)
    PARACLINICAL

 revealed the

    c.150_151del mutation responsible for a loss of function
    GENETICS

.

As in the present case,

    ophthalmological examination
    PARACLINICAL

 is very useful to determine

    Fabry's disease
    DIAGNOSIS

 as a cause of

    young onset stroke
    SYMPTOMS

.

    Females
    GENDER

 may be affected by

    X-linked disease
    GENETICS

, as the

    Fabry's disease
    DIAGNOSIS

.

    Fabry's disease
    DIAGNOSIS

 among

    females
    GENDER

 is mainly characterized by the

    involvement of the nervous and cardiovascular systems
    SYMPTOMS

. The specific treatment is based on an

    enzyme replacement therapy by recombinant enzyme
    MEDICATION

 with

    cardiovascular benefit
    MEDICATION

.

    Despite the presence of cardiovascular risk factors
    NEG_FINDINGS

, this case demonstrates the importance of thorough standardized investigations including

    ophthalmological examination
    PARACLINICAL

 of

    young
    AGE

 patients with

    stroke
    SYMPTOMS

.

Fabry's disease
lysosomal storage disorder
Fabry's disease
hypertrophic concentric cardiomyopathy
Fabry's disease
Fabry's disease
Fabry's disease


Fixed prosthodontic rehabilitation in a wear patient with Fabry's disease.

Fabry's disease is an uncommon X-linked metabolic disorder that leads to abnormal accumulation of glycosphingolipids in the body resulting in a variety of systemic disorders. Few reports have addressed dental findings and management of these patients. This clinical report describes the fixed prosthodontic rehabilitation of an adult male patient with Fabry's disease, who presented with generalized severe wear of the dentition. In addition to numerous systemic morbidities, the patient also presented with intraoral angiokeratomas, telangiactasias, anterior diastemata, bimaxillary prognathism, and other oral findings known to be prominent in these patients. The patient was managed by an interdisciplinary team of dental specialists in close coordination with his nephrologist. The prosthodontic treatment included restorations on all teeth, except mandibular anterior teeth, and the patient was restored with a partial group function scheme of occlusion. At the 3.5-year follow-up appointment, the patient's oral health and integrity of the restorations remained stable. This is the first clinical report describing the prosthodontic management of a patient with Fabry's disease. Unique features related to this patient's fixed prosthodontic treatment include accommodation to complex medical problems, management of maxillary diastemata, and choice of occlusal scheme.

    Fabry's disease
    DIAGNOSIS

 is an

    uncommon X-linked
    GENETICS

    metabolic disorder
    DIAGNOSIS

 that leads to

    abnormal accumulation of glycosphingolipids in the body
    MICROSCOPIC

 resulting in a variety of

    systemic disorders
    SYMPTOMS

. Few reports have addressed dental findings and management of these patients. This clinical report describes the

    fixed prosthodontic rehabilitation
    MEDICATION

 of an

    adult
    AGE

    male
    GENDER

 patient with

    Fabry's disease
    DIAGNOSIS

, who presented with

    generalized severe wear of the dentition
    SYMPTOMS

. In addition to numerous

    systemic morbidities
    SYMPTOMS

, the patient also presented with

    intraoral angiokeratomas
    SYMPTOMS

,

    telangiactasias
    SYMPTOMS

,

    anterior diastemata
    SYMPTOMS

,

    bimaxillary prognathism
    SYMPTOMS

, and other

    oral findings
    SYMPTOMS

 known to be prominent in these patients. The patient was managed by an

    interdisciplinary team of dental specialists
    MEDICATION

 in close coordination with his

    nephrologist
    PARACLINICAL

. The

    prosthodontic treatment included restorations on all teeth, except mandibular anterior teeth
    MEDICATION

, and the patient was

    restored with a partial group function scheme of occlusion
    MEDICATION

. At the 3.5

    -year follow-up appointment
    PARACLINICAL

, the patient's

    oral health and integrity of the restorations remained stable
    SYMPTOMS

. This is the first clinical report describing the

    prosthodontic management
    MEDICATION

 of a patient with

    Fabry's disease
    DIAGNOSIS

. Unique features related to this patient's

    fixed prosthodontic treatment
    MEDICATION

 include accommodation to complex medical problems,

    management of maxillary diastemata
    MEDICATION

, and

    choice of occlusal scheme
    MEDICATION

.

Fabry's disease
metabolic disorder
Fabry's disease
Fabry's disease


Clinical and genetic investigation of a Japanese family with cardiac fabry disease. Identification of a novel α-galactosidase A missense mutation (G195V).

Fabry disease is an X-linked lysosomal storage disorder caused by mutations of the α-galactosidase A gene (GLA), and the disease is a relatively prevalent cause of left ventricular hypertrophy mimicking idiopathic hypertrophic cardiomyopathy. We assessed clinically 5 patients of a three-generation family and also searched for GLA mutations in 10 family members. The proband had left ventricular hypertrophy with localized thinning in the basal posterior wall and late gadolinium enhancement (LGE) in the near-circumferential wall in cardiovascular magnetic resonance images and her sister had vasospastic angina pectoris without organic stenosis of the coronary arteries. LGE notably appeared in parallel with decreased α-galactosidase A activity and increased NT-pro BNP in our patients. We detected a new GLA missense mutation (G195V) in exon 4, resulting in a glycine-to-valine substitution. Of the 10 family members, 5 family members each were positive and negative for this mutation. These new data extend our clinical and molecular knowledge of GLA gene mutations and confirm that a novel missense mutation in the GLA gene is important not only for a precise diagnosis of heterozygous status, but also for confirming relatives who are negative for this mutation.

    Fabry disease
    DIAGNOSIS

 is an

    X-linked
    GENETICS

    lysosomal storage disorder
    DIAGNOSIS

 caused by

    mutations of the α-galactosidase A gene (GLA)
    GENETICS

, and the disease is a relatively prevalent cause of

    left ventricular hypertrophy
    SYMPTOMS

 mimicking

    idiopathic hypertrophic cardiomyopathy
    DIAGNOSIS

. We assessed clinically 5 patients of a

    three-generation family
    FAMILY

 and also searched for

    GLA mutations
    GENETICS

 in 10 family members. The

    proband
    GENDER

 had

    left ventricular hypertrophy
    SYMPTOMS

 with

    localized thinning in the basal posterior wall
    SYMPTOMS

 and

    late gadolinium enhancement (LGE) in the near-circumferential wall
    SYMPTOMS

 in

    cardiovascular magnetic resonance images
    PARACLINICAL

 and

    her
    GENDER

    sister had vasospastic angina pectoris
    FAMILY

    without organic stenosis of the coronary arteries
    NEG_FINDINGS

.

    LGE notably
    SYMPTOMS

 appeared in parallel with

    decreased α-galactosidase A activity
    BIOCHEMICAL

 and

    increased NT-pro BNP
    BIOCHEMICAL

 in our patients. We detected a

    new GLA missense mutation (G195V) in exon 4, resulting in a glycine-to-valine substitution
    GENETICS

. Of the 10 family members,

    5 family members each were positive and negative for this mutation
    FAMILY

. These new data extend our clinical and molecular knowledge of

    GLA gene mutations
    GENETICS

 and confirm that a

    novel missense mutation in the GLA gene
    GENETICS

 is important not only for a precise diagnosis of heterozygous status, but also for confirming

    relatives who are negative for this mutation
    FAMILY

.

Fabry disease
lysosomal storage disorder
idiopathic hypertrophic cardiomyopathy

decreased α-galactosidase A activity
increased NT-pro BNP


Wilhelm Fabry's 1614 report on a giant condyloma of the penis.

For many years it has been the work of Buschke and Löwenstein that has justified calling the exophytic, locally destructive tumour of the anogenital mucosal surface 'giant condyloma of Buschke and Löwenstein' or GCBL. In order to investigate the early history of this rare disease we examined the writings of the barber-surgeon Wilhelm Fabry (1560-1634) who had a serious interest in dermatological disorders and their treatment. We analysed Fabry's 600 Latin case reports and identified the case of a 'monstrous penile tumour'. We then translated this text into English and compared it point by point with later publications. This was followed by a cursory review of surgical treatises from the 16th to the 18th centuries. In 1614 Fabry described and depicted a tumour of the penis; the clinical characteristics (gradual formation of a warty lesion, considerable size, invasive growth, absence of metastases) indicated it was a giant condyloma. His mention of the urethral fistulization enables discrimination from 'common' condylomata acuminata, and the survival period of 10 years after amputation allows exclusion of a 'true' carcinoma. This report is singular among 17th-century case histories. The neoplasias described 300 years later are most probably biologically identical. Thus, Fabry's is the first clinical report; the histological classification, however, belongs to Buschke and Löwenstein. From now on the disease should be designated with the eponym giant condyloma of Fabry-Buschke-Löwenstein or GCFBL.

For many years it has been the work of Buschke and Löwenstein that has justified calling the

    exophytic, locally destructive tumour of the anogenital mucosal surface
    SYMPTOMS

 '

    giant condyloma of Buschke and Löwenstein
    DIAGNOSIS

' or

    GCBL
    DIAGNOSIS

. In order to investigate the early history of this rare disease we examined the writings of the

    barber-surgeon
    PARACLINICAL

 Wilhelm Fabry (1560-1634) who had a serious interest in

    dermatological disorders
    DIAGNOSIS

 and their treatment. We analysed Fabry's 600 Latin case reports and identified the case of a '

    monstrous penile tumour'
    DIAGNOSIS

. We then translated this text into English and compared it point by point with later publications. This was followed by a cursory review of surgical treatises from the 16th to the 18th centuries. In 1614

    Fabry
    PARACLINICAL

 described and depicted a

    tumour of the penis
    SYMPTOMS

; the clinical characteristics (

    gradual formation of a warty lesion
    SYMPTOMS

,

    considerable size
    SYMPTOMS

,

    invasive growth
    SYMPTOMS

,

    absence of metastases
    NEG_FINDINGS

) indicated it was a

    giant condyloma
    DIAGNOSIS

. His mention of the

    urethral fistulization
    SYMPTOMS

 enables discrimination from '

    common' condylomata acuminata
    NEG_FINDINGS

, and the

    survival period of 10 years
    SYMPTOMS

 after

    amputation
    MEDICATION

 allows

    exclusion of a 'true' carcinoma
    NEG_FINDINGS

. This report is singular among 17th-century case histories. The

    neoplasias
    DIAGNOSIS

 described 300 years later are most probably biologically identical. Thus, Fabry's is the first clinical report; the histological classification, however, belongs to Buschke and Löwenstein. From now on the disease should be designated with the eponym

    giant condyloma of Fabry-Buschke-Löwenstein
    DIAGNOSIS

 or

    GCFBL
    DIAGNOSIS

.

absence of metastases
common' condylomata acuminata
exclusion of a 'true' carcinoma


Fabry disease superimposed on overt autoimmune hypothyroidism.

Fabry disease (FD) is an X-linked recessive disorder caused by lysosomal α-galactosidase A deficiency. FD is characterized by the systemic accumulation of globotriaosylceramide with involvement of the heart, kidney, brain and gastrointestinal system. Recently, nonautoimmune thyroid dysfunction was recognized as an additional clinical feature of FD. In the present study, we describe a patient suffering from FD superimposed on overt autoimmune hypothyroidism. The patient was an 11-yr-old boy who presented with goiter and stunted growth, and was diagnosed with primary hypothyroidism due to autoimmune thyroiditis. During levothyroxine replacement therapy, the patient complained of burning pain in his feet and was diagnosed as suffering from FD based on low blood α-galactosidase A activity. In conclusion, we have described the first FD patient preceded by overt autoimmune hypothyroidism.

    Fabry disease (FD)
    DIAGNOSIS

 is an

    X-linked recessive disorder
    GENETICS

 caused by

    lysosomal α-galactosidase A deficiency
    BIOCHEMICAL

.

    FD
    DIAGNOSIS

 is characterized by the

    systemic accumulation of globotriaosylceramide
    MICROSCOPIC

 with

    involvement of the heart, kidney, brain and gastrointestinal system
    MICROSCOPIC

. Recently,

    nonautoimmune thyroid dysfunction
    SYMPTOMS

 was recognized as an additional clinical feature of

    FD
    DIAGNOSIS

. In the present study, we describe a patient suffering from

    FD
    DIAGNOSIS

 superimposed on

    overt autoimmune hypothyroidism
    DIAGNOSIS

. The patient was an

    11-yr-old
    AGE

    boy
    GENDER

 who presented with

    goiter
    SYMPTOMS

 and

    stunted growth
    SYMPTOMS

, and was diagnosed with

    primary hypothyroidism
    DIAGNOSIS

 due to

    autoimmune thyroiditis
    DIAGNOSIS

. During

    levothyroxine replacement therapy
    MEDICATION

, the patient complained of

    burning pain in his feet
    SYMPTOMS

 and was diagnosed as suffering from

    FD
    DIAGNOSIS

 based on

    low blood α-galactosidase A activity
    BIOCHEMICAL

. In conclusion, we have described the first

    FD
    DIAGNOSIS

 patient preceded by

    overt autoimmune hypothyroidism
    DIAGNOSIS

.

Fabry disease (FD)
FD
FD
FD
overt autoimmune hypothyroidism
primary hypothyroidism
autoimmune thyroiditis
FD
FD
overt autoimmune hypothyroidism

lysosomal α-galactosidase A deficiency
low blood α-galactosidase A activity

nonautoimmune thyroid dysfunction
goiter
stunted growth
burning pain in his feet


Left ventricular noncompaction in a patient with fabry disease: overdiagnosis, morphological manifestation of fabry disease or two unrelated rare conditions in the same patient?

We report a clinical case of a young female with Fabry disease but without left ventricular hypertrophy, which fulfills the diagnostic criteria of left ventricular noncompaction (LVNC). To our knowledge, this is the first report of LVNC in a patient with Fabry disease. The possibility of an overdiagnosis of LVNC is discussed based on the limitations of the current diagnostic criteria. This case was further investigated by genetic analysis, which came to demonstrate the limited usefulness of genetic testing in the diagnosis of LVNC. Assuming a true trabecular pattern of LVNC, the hypothesis that the same patient has two unrelated and rare conditions, although possible, is unlikely. The genetic and clinical heterogeneity of LVNC is discussed and supports, along with this clinical case, the hypothesis that LVNC is a morphological expression of different diseases rather than a distinct cardiomyopathy. Accordingly, LVNC could be a rare cardiac manifestation of Fabry disease.

We report a clinical case of a

    young
    AGE

    female
    GENDER

 with

    Fabry disease
    DIAGNOSIS

 but

    without left ventricular hypertrophy
    NEG_FINDINGS

, which fulfills the diagnostic criteria of

    left ventricular noncompaction (LVNC)
    SYMPTOMS

. To our knowledge, this is the first report of

    LVNC
    DIAGNOSIS

 in a patient with

    Fabry disease
    DIAGNOSIS

. The possibility of an

    overdiagnosis
    NEG_FINDINGS

 of

    LVNC
    DIAGNOSIS

 is discussed based on the limitations of the current diagnostic criteria. This case was further investigated by

    genetic analysis
    PARACLINICAL

, which came to demonstrate the

    limited usefulness of genetic testing
    NEG_FINDINGS

 in the diagnosis of

    LVNC
    DIAGNOSIS

. Assuming a true trabecular pattern of

    LVNC
    DIAGNOSIS

, the hypothesis that the same

    patient has two unrelated and rare conditions
    FAMILY

, although possible, is unlikely. The genetic and clinical heterogeneity of

    LVNC
    DIAGNOSIS

 is discussed and supports, along with this clinical case, the hypothesis that

    LVNC
    DIAGNOSIS

 is a morphological expression of different diseases rather than a distinct

    cardiomyopathy
    DIAGNOSIS

. Accordingly,

    LVNC
    DIAGNOSIS

 could be a rare cardiac manifestation of

    Fabry disease
    DIAGNOSIS

.

Fabry disease
LVNC
Fabry disease
LVNC
LVNC
LVNC
LVNC
LVNC
cardiomyopathy
LVNC
Fabry disease

without left ventricular hypertrophy
overdiagnosis
limited usefulness of genetic testing


[Early diagnosis of Fabry disease in children].

Fabry disease, a rare X-linked lysosomal storage disorder, is caused by deficiency of the enzyme α-galactosidase A. The incidence, ranging from one over 40 000 to one over 11 7000 worldwide is probably underestimated due to its unspecific pattern of presentation. The symptoms, including neurological, gastrointestinal, renal, ophthalmological and dermatologic manifestations, start in childhood and adolescence, cause a significant morbidity and are likely to affect the patient's quality of life. Furthermore, Anderson-Fabry disease always progress leading to a multiorgan dysfunction and life-threatening complications with end-stage renal disease, cardiomyopathy and high incidence of stroke. The estimated life in untreated patients is reduced by 15-20 years respectively in men and women. The enzyme replacement therapy, available in Europe from 2001, results in a reduction of major organs failure, morbidity and mortality. We present the case of an 8-year-old male admitted to our Division for overweight with a previous history of acroparesthesias, severe acute pain in hands and feet, abdominal pain, diarrhoea, constipation, bitemporal headache, dyshidrosis, recurrent fever, exercise intolerance and reduced quality of life. The physical examination was within normal limits. The α-galactosidase A activity was deficient in plasma and normal in peripheral leukocytes; the GLA gene showed a nucleotide substitution c.352C>T (p.Arg 118 Cys) in the eson 2 with a residual enzyme activity of the 29% suggesting the diagnosis of Fabry disease. Blood and urine chemistry, the slit-lamp examination and MRI of kidneys, heart and brain excluded any major organ involvement. The enzyme replacement therapy was then started almost three months ago using agasidase alfa at a dose of 0.2 mg/kg infused intravenously every two weeks but, unfortunately, no relief in the symptoms have been reported so far without any severe adverse reactions. This case report aims to point out the importance of an early diagnosis in order to prevent the progression of the disease, the multiorgan failure and to improve the long-term prognosis.

    Fabry disease
    DIAGNOSIS

, a

    rare X-linked
    GENETICS

    lysosomal storage disorder
    DIAGNOSIS

, is caused by deficiency of the enzyme α-galactosidase A. The incidence, ranging from one over 40 000 to one over 11 7000 worldwide is probably underestimated due to its unspecific pattern of presentation. The symptoms, including

    neurological, gastrointestinal, renal, ophthalmological and dermatologic manifestations
    SYMPTOMS

, start in

    childhood
    AGE

 and

    adolescence
    AGE

, cause a significant morbidity and are likely to affect the patient's quality of life. Furthermore,

    Anderson-Fabry disease
    DIAGNOSIS

 always progress leading to a

    multiorgan dysfunction
    SYMPTOMS

 and

    life-threatening complications
    SYMPTOMS

 with

    end-stage renal disease
    SYMPTOMS

,

    cardiomyopathy
    SYMPTOMS

 and high incidence of

    stroke
    SYMPTOMS

. The estimated life in untreated patients is reduced by 15-20 years respectively in

    men
    GENDER

 and

    women
    GENDER

. The

    enzyme replacement therapy
    MEDICATION

, available in Europe from 2001, results in a

    reduction of major organs failure
    SYMPTOMS

,

    morbidity and mortality
    SYMPTOMS

. We present the case of an

    8-year-old
    AGE

    male
    GENDER

 admitted to our Division for

    overweight
    MEDICATION

 with a previous history of

    acroparesthesias
    SYMPTOMS

,

    severe acute pain in hands and feet
    SYMPTOMS

,

    abdominal pain
    SYMPTOMS

,

    diarrhoea
    SYMPTOMS

,

    constipation
    SYMPTOMS

,

    bitemporal headache
    SYMPTOMS

,

    dyshidrosis
    SYMPTOMS

,

    recurrent fever
    SYMPTOMS

,

    exercise intolerance
    SYMPTOMS

 and

    reduced quality of life
    SYMPTOMS

. The

    physical examination was within normal limits
    NEG_FINDINGS

. The

    α-galactosidase A activity was deficient in plasma and normal in peripheral leukocytes
    BIOCHEMICAL

; the

    GLA gene
    GENETICS

 showed a

    nucleotide substitution c.352C>T (p.Arg 118 Cys) in the eson 2 with
    GENETICS

 a

    residual enzyme activity of the 29%
    BIOCHEMICAL

 suggesting the diagnosis of

    Fabry disease
    DIAGNOSIS

.

    Blood and urine chemistry
    PARACLINICAL

, the

    slit-lamp examination
    PARACLINICAL

 and

    MRI of kidneys, heart and brain
    PARACLINICAL

    excluded any major organ involvement
    NEG_FINDINGS

. The

    enzyme replacement therapy
    MEDICATION

 was then started almost three months ago

    using agasidase alfa at a dose of 0.2 mg/kg infused intravenously every two weeks
    MEDICATION

 but, unfortunately,

    no relief in the symptoms
    NEG_FINDINGS

 have been reported so far

    without any severe adverse reactions
    NEG_FINDINGS

. This case report aims to point out the importance of an early diagnosis in order to prevent the progression of the disease, the

    multiorgan failure
    SYMPTOMS

 and to improve the long-term prognosis.

Fabry disease
lysosomal storage disorder
Anderson-Fabry disease
Fabry disease


Mid-ventricular obstruction occurred in hypertrophic left ventricle of heterozygous Fabry's disease-Favorable effects of cibenzoline: A case report.

A 54-year-old woman visited our hospital because of palpitation and dizziness. Systolic ejection murmur, Levine IV/VI, was heard at the left sternal border and atrial gallop was auscultated at apex. Echocardiogram demonstrated diffuse hypertrophy of the left ventricular walls extending to the apex. The left ventricular walls increased symmetrically; the septal and the posterior wall measured approximately 26 mm and 30 mm in thickness, respectively. Apical two-chamber views revealed a narrow outflow of the left ventricular cavity at apex with a distinct convergence zone, where color flow Doppler imaging showed turbulent jet flow from mid to late systole. The leukocyte α-galactosidase A activity was lower than normal. Percutaneous endomyocardial biopsy showed specific change for Fabry's disease by electron microscopy. On cardiac catheterization, mid-ventricular resting pressure gradient of approximately 90 mmHg was shown. This pressure gradient dramatically disappeared after intravenous administration of 70 mg of cibenzoline. We describe a rare case of Fabry's disease that revealed diffuse hypertrophy having dynamic obstruction at mid-left ventricle, like mid-ventricular obstruction, and the administration of cibenzoline had beneficial effects on pressure gradient of mid-left ventricle.

A

    54-year-old
    AGE

    woman
    GENDER

 visited our hospital because of

    palpitation
    SYMPTOMS

 and

    dizziness
    SYMPTOMS

.

    Systolic ejection murmur, Levine IV/VI, was heard at the left sternal border
    SYMPTOMS

 and

    atrial gallop was auscultated at apex
    SYMPTOMS

.

    Echocardiogram
    PARACLINICAL

 demonstrated

    diffuse hypertrophy of the left ventricular walls extending to the apex
    SYMPTOMS

.

    The left ventricular walls increased symmetrically; the septal and the posterior wall measured approximately 26 mm and 30 mm in thickness, respectively
    SYMPTOMS

.

    Apical two-chamber views
    PARACLINICAL

 revealed a

    narrow outflow of the left ventricular cavity at apex with a distinct convergence zone
    SYMPTOMS

, where

    color flow Doppler imaging
    PARACLINICAL

 showed

    turbulent jet flow from mid to late systole
    SYMPTOMS

. The

    leukocyte α-galactosidase A activity was lower than normal
    BIOCHEMICAL

.

    Percutaneous endomyocardial biopsy
    PARACLINICAL

 showed

    specific change for Fabry's disease
    MICROSCOPIC

 by

    electron microscopy
    PARACLINICAL

. On

    cardiac catheterization
    PARACLINICAL

,

    mid-ventricular resting pressure gradient of approximately 90 mmHg
    SYMPTOMS

 was shown. This

    pressure gradient dramatically disappeared
    SYMPTOMS

 after

    intravenous administration of 70 mg of cibenzoline
    MEDICATION

. We describe a rare case of

    Fabry's disease
    DIAGNOSIS

 that revealed

    diffuse hypertrophy having dynamic obstruction at mid-left ventricle, like mid-ventricular obstruction
    SYMPTOMS

, and the

    administration of cibenzoline
    MEDICATION

 had

    beneficial effects on pressure gradient of mid-left ventricle
    SYMPTOMS

.


Diffuse thin glomerular basement membrane in association with Fabry disease in a Chinese female patient.

We report a 41-year-old Chinese female with Fabry disease and diffuse thinning of the glomerular basement membrane (GBM). The patient presented with peripheral edema, mild proteinuria, microscopic hematuria, normal renal function, hypertension and tinnitus. Family screening showed that her daughter had microscopic hematuria, tinnitus and neuropathic pain. Renal biopsy of the proband showed focal segmental glomerulosclerosis with cytoplasmic vacuolization of the glomerular visceral epithelial cells by light microscopy. Laminated myelin inclusions in some of the glomerular podocytes, parietal epithelia, distal tubular epithelial cells and vascular endothelial cells along with diffuse thinning of the GBM (mean thickness of GBM: 216 ± 31 nm) were identified by electron microscopy. Genetic analysis detected a de novo novel GLA mutation, 1208 ins 21 bp, while a new variant of COL4A3 SNP M1209I was carried by mother and daughter as well as the proband's father (I-1) and one sister (II-4). The coexistence of thinned GBM should be considered in patients with Fabry disease-manifested familial hematuria.

We report a

    41-year-old
    AGE

    Chinese
    ETHNICITY

    female
    GENDER

 with

    Fabry disease
    DIAGNOSIS

 and

    diffuse thinning of the glomerular basement membrane (GBM)
    SYMPTOMS

. The patient presented with

    peripheral edema
    SYMPTOMS

,

    mild proteinuria
    BIOCHEMICAL

,

    microscopic hematuria
    BIOCHEMICAL

,

    normal renal function
    NEG_FINDINGS

,

    hypertension
    SYMPTOMS

 and

    tinnitus
    SYMPTOMS

.

    Family screening
    PARACLINICAL

 showed that

    her daughter had microscopic hematuria
    FAMILY

    , tinnitus and neuropathic pain
    FAMILY

.

    Renal biopsy
    PARACLINICAL

 of the proband showed

    focal segmental glomerulosclerosis
    DIAGNOSIS

 with

    cytoplasmic vacuolization of the glomerular visceral epithelial cells
    MICROSCOPIC

 by

    light microscopy
    PARACLINICAL

.

    Laminated myelin inclusions in some of the glomerular podocytes, parietal epithelia, distal tubular epithelial cells and vascular endothelial cells
    MICROSCOPIC

 along with

    diffuse thinning of the GBM (mean thickness of GBM: 216 ± 31 nm)
    MICROSCOPIC

 were identified by

    electron microscopy
    PARACLINICAL

.

    Genetic analysis
    PARACLINICAL

 detected a

    de novo novel GLA mutation, 1208 ins 21 bp,
    GENETICS

 while

    a new variant of COL4A3 SNP M1209I was carried by mother and daughter as well as the proband's father (I-1) and one sister (II-4)
    FAMILY

. The coexistence of

    thinned GBM
    MICROSCOPIC

 should be considered in patients with

    Fabry disease
    DIAGNOSIS

-manifested

    familial hematuria
    SYMPTOMS

.

Fabry disease
focal segmental glomerulosclerosis
Fabry disease


[Diagnostic problems in a 17-year-old patient with gastrointestinal manifestations of Fabry disease].

Fabry disease is a rare X-linked recessive lysosomal storage disorder caused by deficiency of lysosomal enzyme alpha-galactosidase, which leads to accumulation of globotriasylceramides (GL-3) in visceral tissues and vascular endothelium, causing multi-organ failure. We presenta case of Fabry disease in a 17-year-old patient with mainly gastrointestinal manifestations, diagnosed 10 years after the manifestation of first symptoms. Significant and progressive weight loss with abdominal pain and vomiting, leading to cachexia, were observed in early childhood. The patient was investigated for non-inflammatory bowel diseases, Raynaud syndrome, polimyositis, mitochondrial cytopathies, intestinal lypodystrophies and others. The symptoms of intenstinal pseudo-obstruction syndrome were observed and surgical treatment was instituted because of necrosis of the colon. There was progressive cachexia and parenteral nutrition had to be instituted. Finally, plasma alpha-galactosidase was measured, and its deficit confirmed Fabry disease. In conclusion gastrointestinal symptoms in the course of Fabry disease can obscure other characteristic symptoms, may be prodromal and leading. Heart and renal failure may not occur in children. Unexplained abdominal pain and malnutrition may be gastrointestinal manifestations of metabolic disorders.

    Fabry disease
    DIAGNOSIS

 is a

    rare X-linked recessive
    GENETICS

    lysosomal storage disorder
    DIAGNOSIS

 caused by

    deficiency of lysosomal enzyme alpha-galactosidase
    BIOCHEMICAL

, which leads to

    accumulation of globotriasylceramides (GL-3) in visceral tissues and vascular endothelium
    MICROSCOPIC

, causing

    multi-organ failure
    SYMPTOMS

. We presenta case of

    Fabry disease
    DIAGNOSIS

 in a

    17-year-old
    AGE

 patient with

    mainly gastrointestinal manifestations
    SYMPTOMS

, diagnosed 10 years after the manifestation of first symptoms.

    Significant and progressive weight loss
    SYMPTOMS

 with

    abdominal pain
    SYMPTOMS

 and

    vomiting
    SYMPTOMS

, leading to

    cachexia
    SYMPTOMS

, were observed in

    early childhood
    AGE

. The patient was investigated for

    non-inflammatory bowel diseases
    DIAGNOSIS

,

    Raynaud syndrome
    DIAGNOSIS

,

    polimyositis
    DIAGNOSIS

,

    mitochondrial cytopathies
    DIAGNOSIS

,

    intestinal lypodystrophies
    DIAGNOSIS

 and others. The

    symptoms of intenstinal pseudo-obstruction syndrome
    SYMPTOMS

 were observed and

    surgical treatment
    MEDICATION

 was instituted because of

    necrosis of the colon
    SYMPTOMS

. There was

    progressive cachexia
    SYMPTOMS

 and

    parenteral nutrition
    MEDICATION

 had to be instituted. Finally,

    plasma alpha-galactosidase was measured
    BIOCHEMICAL

, and its deficit confirmed

    Fabry disease
    DIAGNOSIS

. In conclusion

    gastrointestinal symptoms
    SYMPTOMS

 in the course of

    Fabry disease
    DIAGNOSIS

 can obscure other characteristic symptoms, may be prodromal and leading.

    Heart and renal failure
    SYMPTOMS

 may not occur in

    children
    AGE

.

    Unexplained abdominal pain
    SYMPTOMS

 and

    malnutrition
    SYMPTOMS

 may be

    gastrointestinal manifestations
    SYMPTOMS

 of

    metabolic disorders
    DIAGNOSIS

.

Fabry disease
lysosomal storage disorder
Fabry disease
non-inflammatory bowel diseases
Raynaud syndrome
polimyositis
mitochondrial cytopathies
intestinal lypodystrophies
Fabry disease
Fabry disease
metabolic disorders


Progressive renal failure despite long-term biweekly enzyme replacement therapy in a patient with Fabry disease secondary to a new α-galactosidase mutation of Leu311Arg (L311R).

A 37-year-old Japanese man affected by Fabry disease secondary to a novel mutation of Leu311Arg (L311R) in α-galactosidase demonstrated progressive renal failure despite biweekly enzyme replacement therapy (ERT) for approximately 10 years. Kidney biopsy revealed foamy glomerular epithelial cells, compatible with the typical pathologic features of Fabry disease. The patient entered a phase III study of Replagal (agalsidase alfa) in 2001, allowing him to continue ERT with biweekly dosing for almost 10 years. During 2 years of that period, he was continued on Fabrazyme (agalsidase beta) biweekly dosing. His estimated GFR was calculated to decrease by 9.9 mL/min/1.73 m(2) per year. Patients with Fabry disease have been reported to have a mean decrease in GFR of 12.2 ± 8.1 mL/min/1.73 m(2) per year. This result suggests that biweekly ERT is only mildly effective at preventing loss of kidney function.

A

    37-year-old
    AGE

    Japanese
    ETHNICITY

    man
    GENDER

 affected by

    Fabry disease
    DIAGNOSIS

 secondary to a

    novel mutation of Leu311Arg (L311R) in α-galactosidase
    GENETICS

 demonstrated

    progressive renal failure
    SYMPTOMS

    despite biweekly enzyme replacement therapy (ERT) for approximately 10 years
    NEG_FINDINGS

.

    Kidney biopsy
    PARACLINICAL

 revealed

    foamy glomerular epithelial cells, compatible with the typical pathologic features of Fabry disease
    MICROSCOPIC

. The patient

    entered a phase III study of Replagal (agalsidase alfa)
    MEDICATION

 in 2001, allowing

    him
    GENDER

 to

    continue ERT with biweekly dosing for almost 10 years
    MEDICATION

. During 2 years of that period,

    he
    GENDER

 was

    continued on Fabrazyme (agalsidase beta) biweekly dosing
    MEDICATION

. His

    estimated GFR was calculated to decrease by 9.9 mL/min/1.73 m(2) per year
    BIOCHEMICAL

. Patients with

    Fabry disease
    DIAGNOSIS

 have been reported to have a

    mean decrease in GFR of 12.2 ± 8.1 mL/min/1.73 m(2) per year
    BIOCHEMICAL

. This result suggests that

    biweekly ERT
    MEDICATION

 is only mildly effective at preventing

    loss of kidney function
    BIOCHEMICAL

.


A case of Fabry's disease with congenital agammaglobulinemia.

Fabry's disease is an X-linked lysosomal storage disorder caused by abnormalities in the α-galactosidase A (GLA) gene, which leads to a GLA deficiency and to the intracellular deposition of globotriaosylceramide (Gb3) within vascular endothelium and other tissues. It manifests as progressive multiple organ dysfunctions caused by the deposition of Gb3. On the other hand, congenital agammaglobulinemia is usually caused by mutations in Bruton's tyrosine kinase (Btk) gene with X-linked dominence, suppresses B cell maturation, and causes recurrent pyogenic infections. In former reports, the distance between the loci in the Xq22 region of the human X chromosome was found to be about 69 kilobases. A 23-yr-old man diagnosed with congenital agammaglobulinemia at age 5, showed typical clinical and laboratory and histopathological findings of Fabry's disease. The genetic basis of this combination of the two syndromes was studied in this patient. Here, we report a case of Fabry's disease with congenital agammaglobulinemia.

    Fabry's disease
    DIAGNOSIS

 is an

    X-linked
    GENETICS

    lysosomal storage disorder
    DIAGNOSIS

 caused by

    abnormalities in the α-galactosidase A (GLA) gene
    GENETICS

, which leads to a

    GLA deficiency
    BIOCHEMICAL

 and to the

    intracellular deposition of globotriaosylceramide (Gb3) within vascular endothelium and other tissues
    MICROSCOPIC

. It manifests as

    progressive multiple organ dysfunctions
    SYMPTOMS

 caused by the

    deposition of Gb3
    MICROSCOPIC

. On the other hand,

    congenital agammaglobulinemia
    DIAGNOSIS

 is usually caused by

    mutations in Bruton's tyrosine kinase (Btk) gene with X-linked dominence
    GENETICS

,

    suppresses B cell maturation
    BIOCHEMICAL

, and causes

    recurrent pyogenic infections
    SYMPTOMS

. In former reports, the

    distance between the loci in the Xq22 region of the human X chromosome
    GENETICS

 was found to be about

    69 kilobases
    GENETICS

. A

    23-yr-old
    AGE

    man
    GENDER

 diagnosed with

    congenital agammaglobulinemia
    DIAGNOSIS

 at

    age 5
    AGE

, showed

    typical clinical and laboratory and histopathological findings
    SYMPTOMS

 of

    Fabry's disease
    DIAGNOSIS

. The genetic basis of this

    combination of the two syndromes
    DIAGNOSIS

 was studied in this patient. Here, we report a case of

    Fabry's disease with congenital agammaglobulinemia
    DIAGNOSIS

.

GLA deficiency
suppresses B cell maturation


Diagnostic dilemma: a young woman with Fabry disease symptoms, no family history, and a "sequencing cryptic" α-galactosidase a large deletion.

Fabry disease, an X-linked lysosomal storage disorder, results from the deficient activity of α-galactosidase A (α-Gal A). In affected males, the clinical diagnosis is confirmed by the markedly decreased α-Gal A activity. However, in female heterozygotes, the α-Gal A activity can range from low to normal due to random X-chromosomal inactivation, and diagnostic confirmation requires identification of the family's α-Gal A gene mutation. In a young female who had occasional acroparesthesias, corneal opacities, and 15 to 50% of the lower limit of normal leukocyte α-Gal A activity, α-Gal A sequencing in two expert laboratories did not identify a confirmatory mutation, presenting a diagnostic dilemma. A renal biopsy proved diagnostic and renewed efforts to detect an α-Gal A mutation. Subsequent gene dosage analyses identified a large α-Gal A deletion confirming her heterozygosity, and she was started on enzyme replacement therapy. Thus, gene dosage analyses can detect large deletions (>50bp) in suspect heterozygotes for X-linked and autosomal dominant diseases that are "sequencing cryptic," resolving molecular diagnostic dilemmas.

    Fabry disease
    DIAGNOSIS

, an

    X-linked
    GENETICS

    lysosomal storage disorder
    DIAGNOSIS

, results from the

    deficient activity of α-galactosidase A (α-Gal A)
    BIOCHEMICAL

. In affected

    males
    GENDER

, the clinical diagnosis is confirmed by the

    markedly decreased α-Gal A activity
    BIOCHEMICAL

. However, in

    female
    GENDER

    heterozygotes
    GENETICS

,

    the α-Gal A activity can range from low to normal
    BIOCHEMICAL

 due to

    random X-chromosomal inactivation
    GENETICS

, and diagnostic confirmation requires identification of the

    family's α-Gal A gene mutation
    FAMILY

. In a

    young
    AGE

    female
    GENDER

 who had

    occasional acroparesthesias
    SYMPTOMS

,

    corneal opacities
    SYMPTOMS

, and

    15 to 50% of the lower limit of normal leukocyte α-Gal A activity
    BIOCHEMICAL

,

    α-Gal A sequencing in two expert laboratories
    PARACLINICAL

    did not identify a confirmatory mutation
    NEG_FINDINGS

, presenting a diagnostic dilemma. A

    renal biopsy
    PARACLINICAL

 proved diagnostic and renewed efforts to detect an

    α-Gal A mutation
    GENETICS

. Subsequent

    gene dosage analyses
    PARACLINICAL

 identified a

    large α-Gal A deletion
    GENETICS

 confirming her

    heterozygosity
    GENETICS

, and

    she
    GENDER

 was started on

    enzyme replacement therapy
    MEDICATION

. Thus,

    gene dosage analyses
    PARACLINICAL

 can detect

    large deletions (>50bp)
    GENETICS

 in

    suspect heterozygotes for X-linked and autosomal dominant diseases
    GENETICS

 that are "sequencing cryptic," resolving molecular diagnostic dilemmas.

Fabry disease
lysosomal storage disorder

occasional acroparesthesias
corneal opacities


Fabry disease 'The New Great Imposter': results of the French Observatoire in Internal Medicine Departments (FIMeD).

Fabry disease (FD) is an X-linked lysosomal storage disorder due to α-galactosidase A deficiency. It is associated with a broad range of clinical symptoms, resulting in frequent misdiagnosis and diagnostic delay, which may impact on patient outcomes. This retrospective observational study of 58 FD patients referred to 10 internal medicine departments in France aimed to review differential diagnoses received prior to diagnosis and examines diagnostic delay. The average age at the time of diagnosis was 27.6 years (range: 10-60) and 42.2 years (range: 9-77) among the 23 males and 35 females analyzed, respectively. Most common symptoms that led to FD diagnosis were family history of FD (12 males and 27 females), followed by pain in extremities (10 males and 5 females), and angiokeratoma (8 males and 4 females). Eighteen patients had received alternative diagnoses prior to FD diagnosis, including a female patient with four previous diagnoses. Four case reports are presented, which illustrate the diagnostic 'odyssey' and delayed diagnosis often experienced by patients. Clinicians should consider a diagnosis of FD when presented with a wide range of symptoms, thus helping to shorten the diagnostic delay and facilitating early therapy with enzyme replacement therapy to improve patient outcomes.

    Fabry disease (FD)
    DIAGNOSIS

 is an

    X-linked
    GENETICS

    lysosomal storage disorder
    DIAGNOSIS

 due to

    α-galactosidase A deficiency
    BIOCHEMICAL

. It is associated with a broad range of clinical symptoms, resulting in frequent misdiagnosis and diagnostic delay, which may impact on patient outcomes. This retrospective observational study of 58

    FD
    DIAGNOSIS

 patients referred to 10 internal medicine departments in

    France
    ETHNICITY

 aimed to review

    differential diagnoses
    PARACLINICAL

 received prior to diagnosis and examines diagnostic delay. The

    average age at the time of diagnosis was 27.6 years (range: 10-60) and 42.2 years (range: 9-77)
    AGE

 among the 23

    males
    GENDER

 and 35

    females
    GENDER

 analyzed, respectively. Most common symptoms that led to

    FD
    DIAGNOSIS

 diagnosis were

    family history of FD
    FAMILY

 (12

    males
    GENDER

 and 27

    females
    GENDER

), followed by

    pain in extremities
    SYMPTOMS

 (10

    males
    GENDER

 and 5

    females
    GENDER

), and

    angiokeratoma
    SYMPTOMS

 (8

    males
    GENDER

 and 4

    females
    GENDER

). Eighteen patients had received alternative diagnoses prior to

    FD
    DIAGNOSIS

 diagnosis, including a

    female
    GENDER

 patient with four previous diagnoses. Four case reports are presented, which illustrate the diagnostic 'odyssey' and delayed diagnosis often experienced by patients. Clinicians should consider a diagnosis of

    FD
    DIAGNOSIS

 when presented with a wide range of symptoms, thus helping to shorten the diagnostic delay and facilitating

    early therapy with enzyme replacement therapy
    MEDICATION

 to improve patient outcomes.

Fabry disease (FD)
lysosomal storage disorder
FD
FD
FD
FD


Fabry disease and Factor V Leiden: a potent vascular risk combination.

A 45-year-old man with heterozygous Factor V Leiden presented with his third cerebrovascular accident despite being on warfarin at a therapeutic international normalized ratio. Subsequent investigation revealed a second genetic diagnosis of Fabry disease. He then had an acute myocardial infarction whilst on aspirin and warfarin.

A

    45-year-old
    AGE

    man
    GENDER

 with

    heterozygous Factor V Leiden
    GENETICS

 presented with his

    third cerebrovascular accident
    SYMPTOMS

    despite being on warfarin at a therapeutic international normalized ratio
    NEG_FINDINGS

. Subsequent investigation revealed a second genetic diagnosis of

    Fabry disease
    DIAGNOSIS

.

    He
    GENDER

 then had an

    acute myocardial infarction
    SYMPTOMS

 whilst on

    aspirin and warfarin
    MEDICATION

.

third cerebrovascular accident
acute myocardial infarction


A family with Fabry disease diagnosed by a single angiokeratoma.

This case presents a 39-year-old gentleman with a single angiokeratoma on the abdomen. Because of a family history of early onset cardiac disease, testing for Fabry disease was performed and a mis-sense mutation (A143T) in the Fabry gene confirmed the diagnosis. The unusual aspect of this case is that the patient otherwise had normal health. His only detectable abnormality was a high serum creatinine at 116 mmol/L. Two further affected males and four carrier females were detected on family screening. We tested a further five patients with a single angiokeratoma for Fabry disease. In the five tested though, no suggestive personal or family history was given for any of the patients and no further cases were detected. This case highlights the need for vigilance within dermatology clinics to consider Fabry disease even if a solitary angiokeratoma is the only presenting feature. Some patients do display a milder phenotype and thus a detailed family history should always be taken. As in this case, a solitary angiokeratoma and a suspicious family history may be the only clue. Because enzyme replacement therapy is now available, the potential benefits for the patient and their family are high.

This case presents a

    39-year-old
    AGE

    gentleman
    GENDER

 with a

    single angiokeratoma on the abdomen
    SYMPTOMS

. Because of a

    family history of early onset cardiac disease
    FAMILY

, testing for

    Fabry disease
    DIAGNOSIS

 was performed and a

    mis-sense mutation (A143T) in the Fabry gene
    GENETICS

 confirmed the diagnosis. The unusual aspect of this case is that the patient

    otherwise had normal health
    NEG_FINDINGS

.

    His
    GENDER

 only detectable abnormality was a high serum creatinine at 116 mmol/L. Two further affected

    males
    GENDER

 and four carrier

    females
    GENDER

 were detected on

    family screening
    PARACLINICAL

. We tested a further five patients with a

    single angiokeratoma
    SYMPTOMS

 for

    Fabry disease
    DIAGNOSIS

. In the five tested though,

    no suggestive personal or family history was given for any of the patients
    NEG_FINDINGS

 and no further cases were detected. This case highlights the need for vigilance within dermatology clinics to consider

    Fabry disease
    DIAGNOSIS

 even if a

    solitary angiokeratoma
    SYMPTOMS

 is the only presenting feature. Some patients do display a milder phenotype and thus a detailed

    family history
    PARACLINICAL

 should always be taken. As in this case, a

    solitary angiokeratoma
    SYMPTOMS

 and a

    suspicious family history
    FAMILY

 may be the only clue. Because

    enzyme replacement therapy
    MEDICATION

 is now available, the potential benefits for the patient and their family are high.

single angiokeratoma on the abdomen
single angiokeratoma
solitary angiokeratoma
solitary angiokeratoma

Fabry disease
Fabry disease
Fabry disease


[Cardiac involvement in Fabry's disease - typical disease course and diagnostic problems].

Fabry disease is a rare X-linked recessive lysosomal storage disease, which can cause a wide range of systemic symptoms. A deficiency of the enzyme alpha galactosidase A due to mutation causes a glycolipid to accumulate within the blood vessels, other tissues, and organs. This accumulation leads to an impairment of proper heart function. Wide range of symptoms makes diagnosis difficult. We present a case of a 43 year-old male with typical Fabry disease.

    Fabry disease
    DIAGNOSIS

 is a

    rare X-linked recessive
    GENETICS

    lysosomal storage disease
    DIAGNOSIS

, which can cause a wide range of

    systemic symptoms
    SYMPTOMS

. A

    deficiency of the enzyme alpha galactosidase A
    BIOCHEMICAL

 due to

    mutation
    GENETICS

 causes

    a glycolipid to accumulate within the blood vessels, other tissues, and organs
    MICROSCOPIC

. This

    accumulation
    MICROSCOPIC

 leads to an

    impairment of proper heart function
    SYMPTOMS

. Wide range of symptoms makes diagnosis difficult. We present a case of a

    43 year-old
    AGE

    male
    GENDER

 with typical

    Fabry disease
    DIAGNOSIS

.

Fabry disease
lysosomal storage disease
Fabry disease

systemic symptoms
impairment of proper heart function


Late-onset Fabry disease associated with angiokeratoma of Fordyce and multiple cherry angiomas.

Fabry disease (FD) is a lysosomal storage disorder. The prevalence and clinical spectrum is higher than previously thought. The average time between onset of symptoms and diagnosis is 10 years. Early identification of patients is essential to institute enzyme therapy and reduce morbidity. We report the case of a 76-year-old man, who presented with loss of consciousness following exertional chest pain. He was found to have tortuous corneal vessels, > 100 cherry angiomas on his trunk, and angiokeratomas on his scrotum. The latter were indistinguishable from angiokeratoma of Fordyce, a diagnosis reported in 15% of men over the age of 50 years, and generally ignored by them. The patient's α-galactosidase levels were low, and a mutation in exon 5 of the GLA gene was identified on DNA analysis, confirming the diagnosis of FD. This case highlights the importance of considering a diagnosis of FD in all male patients with angiokeratoma. It also raises the question of whether the presence of multiple cherry angiomas in patients with cardiac disease should raise the possible diagnosis of FD.

    Fabry disease (FD)
    DIAGNOSIS

 is a

    lysosomal storage disorder
    DIAGNOSIS

. The prevalence and clinical spectrum is higher than previously thought. The average time between onset of symptoms and diagnosis is 10 years. Early identification of patients is essential to institute

    enzyme therapy
    MEDICATION

 and reduce morbidity. We report the case of a

    76-year-old
    AGE

    man
    GENDER

, who presented with

    loss of consciousness
    SYMPTOMS

 following

    exertional chest pain
    SYMPTOMS

.

    He
    GENDER

 was found to have

    tortuous corneal vessels
    SYMPTOMS

,

    > 100 cherry angiomas on his trunk
    SYMPTOMS

, and

    angiokeratomas on his scrotum
    SYMPTOMS

. The latter were indistinguishable from

    angiokeratoma of Fordyce
    SYMPTOMS

, a diagnosis reported in 15% of

    men
    GENDER

    over the age of 50 years
    AGE

, and generally ignored by them. The patient's

    α-galactosidase levels were low
    BIOCHEMICAL

, and a

    mutation in exon 5 of the GLA gene
    GENETICS

 was identified on

    DNA analysis
    PARACLINICAL

, confirming the diagnosis of

    FD
    DIAGNOSIS

. This case highlights the importance of considering a diagnosis of

    FD
    DIAGNOSIS

 in all

    male
    GENDER

 patients with

    angiokeratoma
    SYMPTOMS

. It also raises the question of whether the presence of

    multiple cherry angiomas
    SYMPTOMS

 in patients with

    cardiac disease
    SYMPTOMS

 should raise the possible diagnosis of

    FD
    DIAGNOSIS

.

Fabry disease (FD)
lysosomal storage disorder
FD
FD
FD

loss of consciousness
exertional chest pain
tortuous corneal vessels
> 100 cherry angiomas on his trunk
angiokeratomas on his scrotum
angiokeratoma of Fordyce
angiokeratoma
multiple cherry angiomas
cardiac disease


Young woman with recurrent ischemic strokes diagnosed as Fabry disease: lessons learned from a case report.

Several epidemiologic studies suggest that Fabry disease should be considered in young patients with cryptogenic stroke. We report a case of a young woman presenting with recurrent ischemic strokes who was finally diagnosed with Fabry disease after impaired kidney function had been identified. Fabry disease should be considered in unexplained cases of first or recurrent strokes in young patients disregarding the gender of the patient, especially when chronic kidney disease and/or proteinuria are present. Renal function should be closely monitored in patients with strokes and followed up after the event. In this case, intravenous thrombolysis was performed after the second ischemic event. No other case of thrombolysis for ischemic stroke in Fabry disease has been described in the literature.

Several epidemiologic studies suggest that

    Fabry disease
    DIAGNOSIS

 should be considered in

    young
    AGE

 patients with

    cryptogenic stroke
    SYMPTOMS

. We report a case of a

    young
    AGE

    woman
    GENDER

 presenting with

    recurrent ischemic strokes
    SYMPTOMS

 who was finally diagnosed with

    Fabry disease
    DIAGNOSIS

 after

    impaired kidney function
    BIOCHEMICAL

 had been identified.

    Fabry disease
    DIAGNOSIS

 should be considered in unexplained cases of

    first or recurrent strokes
    SYMPTOMS

 in

    young
    AGE

 patients disregarding the gender of the patient, especially when

    chronic kidney disease
    DIAGNOSIS

 and/or

    proteinuria
    BIOCHEMICAL

 are present.

    Renal function
    PARACLINICAL

 should be

    closely monitored
    PARACLINICAL

 in patients with

    strokes
    SYMPTOMS

 and followed up after the event. In this case,

    intravenous thrombolysis
    MEDICATION

 was performed after the

    second ischemic event
    SYMPTOMS

. No other case of

    thrombolysis
    MEDICATION

 for

    ischemic stroke
    SYMPTOMS

 in

    Fabry disease
    DIAGNOSIS

 has been described in the literature.

Fabry disease
Fabry disease
Fabry disease
chronic kidney disease
Fabry disease

cryptogenic stroke
recurrent ischemic strokes
first or recurrent strokes
strokes
second ischemic event
ischemic stroke


Fabry's disease and psychosis: causality or coincidence?

A 21-year-old female with Fabry's disease (FD) presented acute psychotic symptoms such as delusions, auditory hallucinations and formal thought disorders. Since the age of 14, she had suffered from various psychiatric symptoms increasing in frequency and intensity. We considered the differential diagnoses of prodromal symptoms of schizophrenia and organic schizophrenia-like disorder. Routine examinations including cognitive testing, electroencephalography and structural magnetic resonance imaging revealed no pathological findings. Additional structural and functional imaging demonstrated a minor CNS involvement of FD, yet without functional limitations. In summary our examination results support the thesis that in the case of our patient a mere coincidence of FD and psychotic symptoms is more likely than a causal connection.

A

    21-year-old
    AGE

    female
    GENDER

 with

    Fabry's disease (FD)
    DIAGNOSIS

 presented

    acute psychotic symptoms such as delusions
    SYMPTOMS

,

    auditory hallucinations
    SYMPTOMS

 and

    formal thought disorders
    SYMPTOMS

. Since the

    age of 14
    AGE

,

    she
    GENDER

 had suffered from

    various psychiatric symptoms
    SYMPTOMS

 increasing in frequency and intensity. We considered the

    differential diagnoses
    PARACLINICAL

 of

    prodromal symptoms of schizophrenia
    SYMPTOMS

 and

    organic schizophrenia-like disorder
    DIAGNOSIS

.

    Routine examinations
    PARACLINICAL

 including

    cognitive testing
    PARACLINICAL

,

    electroencephalography
    PARACLINICAL

 and

    structural magnetic resonance imaging
    PARACLINICAL

 revealed

    no pathological findings
    NEG_FINDINGS

.

    Additional structural and functional imaging
    PARACLINICAL

 demonstrated a

    minor CNS involvement of FD
    SYMPTOMS

, yet

    without functional limitations
    NEG_FINDINGS

. In summary our examination results support the thesis that in the case of our patient a

    mere coincidence of FD and psychotic symptoms
    SYMPTOMS

 is more likely than a causal connection.

Fabry's disease (FD)
organic schizophrenia-like disorder

no pathological findings
without functional limitations


Unexpected Fabry disease in a renal allograft kidney: an underrecognized cause of poor allograft function.

Fabry disease is an X-linked recessive lysosomal storage disease caused by a deficiency of α-galactosidase A, with characteristic ultrastructural cytoplasmic myelin-like inclusions. Renal lesions are seen in male and variably in heterozygous female patients. One previous report has described Fabry disease involving a renal allograft from a deceased female donor with no history of Fabry disease. The authors describe another case, in which suspicion for Fabry disease was raised ultrastructurally. This serves as a reminder that proteinuria after renal transplantation may be due to donor-derived disease. Fabry disease is probably an underrecognized cause of graft dysfunction. This case provides further justification for ultrastructural examination of renal allograft biopsies.

    Fabry disease
    DIAGNOSIS

 is an

    X-linked recessive
    GENETICS

    lysosomal storage disease
    DIAGNOSIS

 caused by a

    deficiency of α-galactosidase A
    BIOCHEMICAL

, with characteristic

    ultrastructural cytoplasmic myelin-like inclusions
    MICROSCOPIC

.

    Renal lesions
    SYMPTOMS

 are seen in

    male
    GENDER

 and variably in

    heterozygous
    GENETICS

    female
    GENDER

 patients. One previous report has described

    Fabry disease
    DIAGNOSIS

 involving a

    renal allograft
    MEDICATION

 from a

    deceased female
    MEDICATION

 donor with

    no history of Fabry disease
    NEG_FINDINGS

. The authors describe another case, in which suspicion for

    Fabry disease
    DIAGNOSIS

 was raised ultrastructurally. This serves as a reminder that

    proteinuria
    BIOCHEMICAL

 after

    renal transplantation
    MEDICATION

 may be due to donor-derived disease.

    Fabry disease
    DIAGNOSIS

 is probably an underrecognized cause of

    graft dysfunction
    SYMPTOMS

. This case provides further justification for

    ultrastructural examination of renal allograft biopsies
    PARACLINICAL

.

Fabry disease
lysosomal storage disease
Fabry disease
Fabry disease
Fabry disease

deficiency of α-galactosidase A
proteinuria

renal allograft
deceased female
renal transplantation


Persistent increase in cardiac troponin I in Fabry disease: a case report.

Hypertrophic cardiomyopathy is a frequent manifestation in Fabry disease (FD) - an X-linked lysosomal storage disorder caused by reduced activity of the enzyme α-galactosidase A. In FD an elevation of specific cardiac biomarkers, such as cardiac troponin I (cTNI) has been reported in case of clinical manifestation suggestive of myocardial ischemia. In diagnosing acute myocardial infarction cTNI is considered the most reliable parameter.

In the referred case we present a 59 years old female patient with the diagnosis of FD presenting with persistently increased cTNI level (lowest value 0.46 ng/ml, highest value 0.69 ng/ml; normal range <0.05 ng/ml) over a period of 5 months lacking cardiac clinical signs. Since renal insufficiency did not explain the degree of cTNI elevation, this was interpreted as a result of cardiac involvement in FD. Cardiac MRI showed marked left ventricular hypertrophy and focal late Gadolinium enhancement.

Our case report demonstrates a persistent cTNI release in FD with cardiac involvement. Proving the persistence in a symptom free interval, it might be related to a direct damage of myocytes. In FD cTNI could serve as a beneficial long term parameter providing new perspectives for screening strategies.

    Hypertrophic cardiomyopathy
    DIAGNOSIS

 is a frequent manifestation in

    Fabry disease (FD)
    DIAGNOSIS

 - an

    X-linked
    GENETICS

    lysosomal storage disorder
    DIAGNOSIS

 caused by reduced activity of the enzyme α-galactosidase A. In

    FD
    DIAGNOSIS

 an

    elevation of specific cardiac biomarkers, such as cardiac troponin I (cTNI)
    BIOCHEMICAL

 has been reported in case of

    clinical manifestation suggestive of myocardial ischemia
    SYMPTOMS

. In diagnosing

    acute myocardial infarction
    SYMPTOMS

    cTNI
    BIOCHEMICAL

 is considered the most reliable parameter.

In the referred case we present a

    59 years old
    AGE

    female
    GENDER

 patient with the diagnosis of

    FD
    DIAGNOSIS

 presenting with

    persistently increased cTNI level (lowest value 0.46 ng/ml, highest value 0.69 ng/ml; normal range <0.05 ng/ml) over a period of 5 months
    BIOCHEMICAL

    lacking cardiac clinical signs
    NEG_FINDINGS

. Since

    renal insufficiency did not explain the degree of cTNI elevation
    NEG_FINDINGS

, this was interpreted as a result of

    cardiac involvement
    SYMPTOMS

 in

    FD
    DIAGNOSIS

.

    Cardiac MRI
    PARACLINICAL

 showed

    marked left ventricular hypertrophy
    SYMPTOMS

 and

    focal late Gadolinium enhancement
    SYMPTOMS

.

Our case report demonstrates a

    persistent cTNI release
    BIOCHEMICAL

 in

    FD
    DIAGNOSIS

 with

    cardiac involvement
    SYMPTOMS

. Proving the

    persistence in a symptom free interval
    SYMPTOMS

, it might be related to a

    direct damage of myocytes
    SYMPTOMS

. In

    FD
    DIAGNOSIS

    cTNI
    BIOCHEMICAL

 could serve as a beneficial long term parameter providing new perspectives for screening strategies.

Hypertrophic cardiomyopathy
Fabry disease (FD)
lysosomal storage disorder
FD
FD
FD
FD
FD


[Fabry's disease revealed by stroke: a case report].

We report a 35-year-old man with a stroke as the presenting feature of Fabry's disease. Cerebrovascular manifestation can be the first manifestation of this disease and must be systematically evoked by the neurologist. The neurological follow-up of these patients must be systematic.

We report a

    35-year-old
    AGE

    man
    GENDER

 with a

    stroke
    SYMPTOMS

 as the presenting feature of

    Fabry's disease
    DIAGNOSIS

.

    Cerebrovascular manifestation
    SYMPTOMS

 can be the first manifestation of this disease and must be systematically evoked by the

    neurologist
    PARACLINICAL

. The

    neurological follow-up
    PARACLINICAL

 of these patients must be systematic.


[Efficacy of replacement enzyme therapy on central nervous system manifestations in Fabry's disease].

Fabry's disease (FD) an X-linked inherited lysosomal sphingolipidosis leads to a multisystemic disease. The efficacy of replacement enzyme therapy on the central nervous system manifestations has not been evaluated.

A 38-year-old patient suffered from a Fabry's disease diagnosed at the age of 10. Since the age of 26, he suffered from repeated ischemic strokes. Since the age of 34, he was treated by enzyme replacement therapy (agalsidase beta, 1 mg/kg/14 days). He had a cerebral MRI evaluation 1 year and 4 years after the initiation of the enzyme therapy. No new clinical event occurred during the follow-up and the imaging did not evidence new lesion.

We report the cerebral MRI follow-up under enzyme replacement therapy in a patient with Fabry's disease with central nervous system involvement. No new lesion appeared.

Enzyme replacement therapy seems beneficial in Fabry's disease with central nervous system involvement.

    Fabry's disease (FD)
    DIAGNOSIS

 an

    X-linked inherited
    GENETICS

    lysosomal sphingolipidosis
    DIAGNOSIS

 leads to a

    multisystemic disease
    DIAGNOSIS

. The efficacy of

    replacement enzyme therapy
    MEDICATION

 on the

    central nervous system manifestations
    SYMPTOMS

 has not been evaluated.

A

    38-year-old
    AGE

 patient suffered from a

    Fabry's disease
    DIAGNOSIS

 diagnosed at the

    age of 10
    AGE

. Since the

    age of 26
    AGE

,

    he
    GENDER

 suffered from

    repeated ischemic strokes
    SYMPTOMS

. Since the

    age of 34
    AGE

,

    he
    GENDER

 was treated by

    enzyme replacement therapy (agalsidase beta, 1 mg/kg/14 days)
    MEDICATION

.

    He
    GENDER

 had a

    cerebral MRI evaluation
    PARACLINICAL

 1 year and 4 years after the

    initiation of the enzyme therapy
    MEDICATION

.

    No new clinical event occurred during the follow-up
    NEG_FINDINGS

 and the

    imaging did not evidence new lesion
    NEG_FINDINGS

.

We report the

    cerebral MRI follow-up
    PARACLINICAL

 under

    enzyme replacement therapy
    MEDICATION

 in a patient with

    Fabry's disease
    DIAGNOSIS

 with

    central nervous system involvement
    SYMPTOMS

.

    No new lesion appeared
    NEG_FINDINGS

.

    Enzyme replacement therapy
    MEDICATION

 seems beneficial in

    Fabry's disease
    DIAGNOSIS

 with

    central nervous system involvement
    SYMPTOMS

.

Fabry's disease (FD)
lysosomal sphingolipidosis
multisystemic disease
Fabry's disease
Fabry's disease
Fabry's disease

central nervous system manifestations
repeated ischemic strokes
central nervous system involvement
central nervous system involvement


[Fabry disease among hypertrophic cardiomyopathy of genetic origin].

Primary hypertrophic cardiomyopathy is a relatively frequent disease (1/500) which results from a mutation in a gene encoding a sarcomeric protein. In a series of 184 cases, nearly half (46 %) were secondary to a mutation in one of the 4 following genes : MYBPC3, MYH7, TNNI3, TNNT2. In Fabry disease, an exclusive or nearly exclusive cardiac expression is possible and referred to as "cardiac variant". The hypertrophic cardiomyopathy of Fabry disease is usually unspecific. Two series reported a prevalence of Fabry disease of about 6% among male cases. An Italian series of 34 female cases with hypertrophic cardiomyopathy demonstrated that it was feasible to diagnose Fabry disease in females by screening for specific lesions in myocardial biopsies. We detected a patient who initially presented with a common hypertrophic cardiomyopathy except that his ECG showed depression of ST segment and inversion of T wave in leads D1, VL and in precordial leads. The family history revealed several affected relatives and female carriers. In conclusion, an isolated common hypertrophic cardiomyopathy may be secondary to Fabry disease. Male patients should be screened systemically for enzyme defect except in cases of father-to-son transmission. In females, an affected male relative should be searched for screening or the GLA gene should be sequenced. It is important to think about a putative Fabry disease in cases with hypertrophic cardiomyopathy not associated with any obvious cause.

    Primary hypertrophic cardiomyopathy
    DIAGNOSIS

 is a relatively frequent disease (1/500) which results from a

    mutation in a gene encoding a sarcomeric protein
    GENETICS

. In a series of 184 cases, nearly half (46 %) were secondary to a

    mutation in one of the 4 following genes : MYBPC3, MYH7, TNNI3, TNNT2
    GENETICS

. In

    Fabry disease
    DIAGNOSIS

, an

    exclusive or nearly exclusive cardiac expression
    SYMPTOMS

 is possible and referred to as "

    cardiac variant"
    SYMPTOMS

. The

    hypertrophic cardiomyopathy
    SYMPTOMS

 of

    Fabry disease
    DIAGNOSIS

 is usually unspecific. Two series reported a prevalence of

    Fabry disease
    DIAGNOSIS

 of about 6% among

    male
    GENDER

 cases. An

    Italian
    ETHNICITY

 series of 34

    female
    GENDER

 cases with

    hypertrophic cardiomyopathy
    DIAGNOSIS

 demonstrated that it was feasible to diagnose

    Fabry disease
    DIAGNOSIS

 in

    females
    GENDER

 by screening for

    specific lesions in myocardial biopsies
    SYMPTOMS

. We detected a patient who initially presented with a

    common hypertrophic cardiomyopathy
    SYMPTOMS

 except that

    his
    GENDER

    ECG
    SYMPTOMS

 showed

    depression of ST segment and inversion of T wave in leads D1, VL and in precordial leads
    SYMPTOMS

. The

    family history revealed several affected relatives and female carriers
    FAMILY

. In conclusion, an

    isolated common hypertrophic cardiomyopathy
    SYMPTOMS

 may be secondary to

    Fabry disease
    DIAGNOSIS

.

    Male
    GENDER

 patients should be screened systemically for

    enzyme defect
    PARACLINICAL

 except in cases of

    father-to-son transmission
    FAMILY

. In

    females
    GENDER

, an affected

    male
    GENDER

 relative should be searched for screening or the

    GLA gene
    PARACLINICAL

 should be sequenced. It is important to think about a putative

    Fabry disease
    DIAGNOSIS

 in cases with

    hypertrophic cardiomyopathy
    SYMPTOMS

    not associated with any obvious cause
    NEG_FINDINGS

.

Primary hypertrophic cardiomyopathy
Fabry disease
Fabry disease
Fabry disease
hypertrophic cardiomyopathy
Fabry disease
Fabry disease
Fabry disease


[Diagnosis of Fabry disease: usefulness of the clinical investigation].

Fabry disease, an X-linked lysosomal storage disorder due to alpha-galactosidase A deficiency, leads to an accumulation of globotriaosylceramide resulting in a multisystemic disorder. The initial manifestations of the disease are not specific, leading to a delayed diagnosis. We report a patient in whom the diagnosis was obtained by family screening and the confrontation of clinical signs. We also present a 4 year follow-up under enzyme replacement therapy (agalsidase β, 1 mg/kg/14 days).

    Fabry disease
    DIAGNOSIS

, an

    X-linked
    GENETICS

    lysosomal storage disorder
    DIAGNOSIS

 due to

    alpha-galactosidase A deficiency
    BIOCHEMICAL

, leads to an

    accumulation of globotriaosylceramide
    MICROSCOPIC

 resulting in a

    multisystemic disorder
    DIAGNOSIS

. The initial manifestations of the disease are not specific, leading to a delayed diagnosis. We report a patient in whom the diagnosis was obtained by

    family screening
    PARACLINICAL

 and the confrontation of clinical signs. We also present a 4 year follow-up under

    enzyme replacement therapy (agalsidase β, 1 mg/kg/14 days)
    MEDICATION

.

Fabry disease
lysosomal storage disorder
multisystemic disorder


[Priapism: a severe paediatric complication of Fabry disease].

Fabry disease is an X-linked recessive lysosomal storage disorder caused by α-galactosidase A deficiency. Although the disease presents in childhood, diagnosis is often delayed to adulthood or missed, presumably due to the lack of specificity of the symptoms and to the absence of major complication during the paediatric years. We report a 9-year-old boy known to have a Fabry disease who presented an episode of priapism. Successful treatment was achieved by repeated corporeal aspiration under general anaesthesia. This case is the fifth report of priapism in children with Fabry disease, suggesting that priapism may be a severe vascular complication of the disease during infancy. This report emphasizes the importance of an early diagnosis and treatment of Fabry disease, including enzyme replacement therapy, to prevent major disease-associated morbidity and to optimize patient outcomes.

    Fabry disease
    DIAGNOSIS

 is an

    X-linked recessive
    GENETICS

    lysosomal storage disorder
    DIAGNOSIS

 caused by

    α-galactosidase A deficiency
    BIOCHEMICAL

. Although the disease presents in

    childhood
    AGE

, diagnosis is often delayed to

    adulthood
    AGE

 or missed, presumably due to the lack of specificity of the symptoms and to the absence of major complication during the

    paediatric years
    AGE

. We report a

    9-year-old
    AGE

    boy
    GENDER

 known to have a

    Fabry disease
    DIAGNOSIS

 who presented an episode of

    priapism
    SYMPTOMS

. Successful treatment was achieved by

    repeated corporeal aspiration under general anaesthesia
    MEDICATION

. This case is the fifth report of

    priapism
    SYMPTOMS

 in

    children
    AGE

 with

    Fabry disease
    DIAGNOSIS

, suggesting that

    priapism
    SYMPTOMS

 may be a

    severe vascular complication
    SYMPTOMS

 of the disease during

    infancy
    AGE

. This report emphasizes the importance of an early diagnosis and treatment of

    Fabry disease
    DIAGNOSIS

, including

    enzyme replacement therapy
    MEDICATION

, to prevent

    major disease-associated morbidity
    SYMPTOMS

 and to optimize patient outcomes.

Fabry disease
lysosomal storage disorder
Fabry disease
Fabry disease
Fabry disease

priapism
priapism
priapism
severe vascular complication
major disease-associated morbidity


[Azoospermia as a new feature of Fabry disease].

This case report describes two cases of azoospermia in men suffering from Fabry disease. Testicular biopsies revealed characteristic aspects of trihexosid ceramid deposit in the Leydig cells by optic and electronic microscopic analysis. Using TESE and ICSI, sperm retrieval led to pregnancies and deliveries of healthy children. Azoospermia should be considered as a possible complication of Fabry disease and we recommend a routine sperm analysis in the follow up of young patients with Fabry disease. As we do not know the efficacy of the agalsidase therapy on the genital issue of the Fabry disease, consideration of sperm cryopreservation is suggested.

This case report describes two cases of

    azoospermia
    DIAGNOSIS

 in

    men
    GENDER

 suffering from

    Fabry disease
    DIAGNOSIS

.

    Testicular biopsies
    PARACLINICAL

 revealed

    characteristic aspects of trihexosid ceramid deposit in the Leydig cells
    MICROSCOPIC

 by

    optic and electronic microscopic analysis
    PARACLINICAL

. Using

    TESE
    MEDICATION

 and

    ICSI
    MEDICATION

,

    sperm retrieval
    MEDICATION

 led to

    pregnancies
    SYMPTOMS

 and

    deliveries of healthy children
    MEDICATION

.

    Azoospermia
    BIOCHEMICAL

 should be considered as a possible complication of

    Fabry disease
    DIAGNOSIS

 and we recommend a

    routine sperm analysis
    PARACLINICAL

 in the follow up of

    young
    AGE

 patients with

    Fabry disease
    DIAGNOSIS

. As we do not know the efficacy of the

    agalsidase therapy
    MEDICATION

 on the genital issue of the

    Fabry disease
    DIAGNOSIS

, consideration of

    sperm cryopreservation
    MEDICATION

 is suggested.

azoospermia
Fabry disease
Fabry disease
Fabry disease
Fabry disease

TESE
ICSI
sperm retrieval
deliveries of healthy children
agalsidase therapy
sperm cryopreservation


Poikilothermia in a 38-year-old Fabry patient.

A Fabry patient with poikilothermia is described. Laboratory investigations, neuro-imaging and autonomic function tests did not disclose a cause. Assessment of intra-epidermal nerve fibre density and quantitative sensory testing revealed small fibre neuropathy with a highly impaired cold sensation. We speculate that the poikilothermia is either caused by a vascular lesion in the hypothalamus not visible on MRI or by small fibre neuropathy leading to disturbed body temperature perception and therefore impaired thermoregulation.

A

    Fabry
    DIAGNOSIS

 patient with

    poikilothermia
    SYMPTOMS

 is described.

    Laboratory investigations
    PARACLINICAL

,

    neuro-imaging
    PARACLINICAL

 and

    autonomic function tests
    PARACLINICAL

    did not disclose a cause
    NEG_FINDINGS

.

    Assessment of intra-epidermal nerve fibre density
    PARACLINICAL

 and

    quantitative sensory testing
    PARACLINICAL

 revealed

    small fibre neuropathy
    DIAGNOSIS

 with a

    highly impaired cold sensation
    SYMPTOMS

. We speculate that the

    poikilothermia
    SYMPTOMS

 is either caused by a

    vascular lesion in the hypothalamus not visible on MRI
    SYMPTOMS

 or by

    small fibre neuropathy
    DIAGNOSIS

 leading to

    disturbed body temperature perception
    SYMPTOMS

 and therefore

    impaired thermoregulation
    SYMPTOMS

.

Fabry
small fibre neuropathy
small fibre neuropathy


Cardiac magnetic resonance imaging illustrating Anderson-Fabry disease progression.

Anderson-Fabry disease is an X-linked lysosomal storage disorder resulting from a deficiency of the enzyme α-galactosidase A (α-Gal A) and subsequent cellular storage of the enzyme's substrate globotriaosylceramide (Gb3) and related glycosphingolipids. We report a case of Anderson-Fabry disease with cardiac involvement evaluated with cardiovascular MRI. Disease progression was observed despite enzyme replacement therapy.

    Anderson-Fabry disease
    DIAGNOSIS

 is an

    X-linked
    GENETICS

    lysosomal storage disorder
    DIAGNOSIS

 resulting from a

    deficiency of the enzyme α-galactosidase A (α-Gal A)
    BIOCHEMICAL

 and subsequent

    cellular storage of the enzyme's substrate globotriaosylceramide (Gb3) and related glycosphingolipids
    MICROSCOPIC

. We report a case of

    Anderson-Fabry disease
    DIAGNOSIS

 with

    cardiac involvement
    SYMPTOMS

 evaluated with

    cardiovascular MRI
    PARACLINICAL

.

    Disease progression
    SYMPTOMS

 was observed

    despite enzyme replacement therapy
    NEG_FINDINGS

.

Anderson-Fabry disease
lysosomal storage disorder
Anderson-Fabry disease


Fabry disease exhibiting recurrent stroke and persistent inflammation.

We describe two cases of Fabry disease in non-blood-related Japanese men, manifesting recurrent stroke even after the start of enzyme replacement therapy. Both exhibited chronic inflammation and ocular involvement with elevated levels of serum C reactive protein prior to the onset of stroke. We, therefore, suggest the association among persistent inflammation, ocular involvement and recurrent stroke in a certain subset of Fabry disease patients. Both cases received enzyme replacement therapy with no improvement in inflammatory signs or laboratory data. These cases suggest that Fabry disease should be considered in young patients with cryptogenic stroke or CNS manifestations and fever of unknown origin.

We describe two cases of

    Fabry disease
    DIAGNOSIS

 in

    non-blood-related
    NEG_FINDINGS

    Japanese
    ETHNICITY

    men
    GENDER

, manifesting

    recurrent stroke
    SYMPTOMS

    even after the start of enzyme replacement therapy
    NEG_FINDINGS

. Both exhibited

    chronic inflammation
    SYMPTOMS

 and

    ocular involvement
    SYMPTOMS

 with

    elevated levels of serum C reactive protein
    BIOCHEMICAL

 prior to the onset

    of stroke
    SYMPTOMS

. We, therefore, suggest the association among

    persistent inflammation
    SYMPTOMS

,

    ocular involvement
    SYMPTOMS

 and

    recurrent stroke
    SYMPTOMS

 in a certain subset of

    Fabry disease
    DIAGNOSIS

 patients. Both cases received

    enzyme replacement therapy
    MEDICATION

 with

    no improvement in inflammatory signs or laboratory data
    NEG_FINDINGS

. These cases suggest that

    Fabry disease
    DIAGNOSIS

 should be considered in

    young
    AGE

 patients with

    cryptogenic stroke
    SYMPTOMS

 or

    CNS manifestations
    SYMPTOMS

 and

    fever of unknown origin
    SYMPTOMS

.

recurrent stroke
chronic inflammation
ocular involvement
of stroke
persistent inflammation
ocular involvement
recurrent stroke
cryptogenic stroke
CNS manifestations
fever of unknown origin


Electron microscopy in end stage renal disease: a case of Fabry's disease.

Fabry's disease is an X-linked error of metabolism with deficiency of the enzyme α-glycosidase A, and glycosphingolipid accumulation in multiple tissues. Patients may be asymptomatic and present with advanced disease. We report a case of a 38 year old white male who presented with end stage renal disease of unknown etiology. He received a living-related donor kidney transplant (mother), but lost the graft after 10 years to multiple episodes of rejection. Review of the native renal biopsy with added ultrastructural studies established the diagnosis of Fabry's disease. Evaluation of renal biopsies showing advanced chronic injury should include electron microscopic studies, which may reveal characteristic diagnostic features, as seen in this case of Fabry's disease. Identification of hereditary disorders involving the kidney is important for appropriate treatment and prevention of disease recurrence. Potential living related donors should be screened for genetic involvement.

    Fabry's disease
    DIAGNOSIS

 is an

    X-linked error of metabolism
    GENETICS

 with

    deficiency of the enzyme &#x03B1;-glycosidase A
    BIOCHEMICAL

, and

    glycosphingolipid accumulation in multiple tissues
    MICROSCOPIC

. Patients may be

    asymptomatic
    NEG_FINDINGS

 and present with advanced disease. We report a case of a

    38 year old
    AGE

    white
    ETHNICITY

    male
    GENDER

 who presented with

    end stage renal disease of unknown etiology
    DIAGNOSIS

.

    He
    GENDER

    received a living-related donor kidney transplant (mother)
    MEDICATION

, but

    lost the graft after 10 years
    NEG_FINDINGS

 to

    multiple episodes of rejection
    SYMPTOMS

.

    Review of the native renal biopsy
    PARACLINICAL

 with

    added ultrastructural studies
    PARACLINICAL

 established the diagnosis of

    Fabry's disease
    DIAGNOSIS

.

    Evaluation of renal biopsies
    PARACLINICAL

 showing

    advanced chronic injury
    MICROSCOPIC

 should include

    electron microscopic studies
    PARACLINICAL

, which may reveal characteristic diagnostic features, as seen in this case of

    Fabry's disease
    DIAGNOSIS

. Identification of

    hereditary disorders involving the kidney
    DIAGNOSIS

 is important for appropriate treatment and prevention of disease recurrence. Potential living related donors should be screened for

    genetic involvement
    GENETICS

.

X-linked error of metabolism
genetic involvement

asymptomatic
lost the graft after 10 years


[Females with Fabry's disease - an interdisciplinary diagnostic and therapeutic challenge].

Fabry's disease is a rare genetic storage disorder leading to an accumulation of globotriaosylceramides in the lysosomes of various organs. Being X-chromosomal-linked, most studies in the past focused on involvement in male patients. However, it has been elucidated recently that female patients can present typical organ involvement and, thus, have to be treated respectively. This synopsis wants to systematically review the typical organ involvement in female Fabry patients. Moreover, therapy recommendations especially for female patients are discussed.

    Fabry's disease
    DIAGNOSIS

 is a

    rare genetic storage disorder
    DIAGNOSIS

 leading to an

    accumulation of globotriaosylceramides in the lysosomes of various organs
    MICROSCOPIC

. Being

    X-chromosomal-linked
    GENETICS

, most studies in the past focused on involvement in

    male
    GENDER

 patients. However, it has been elucidated recently that

    female
    GENDER

 patients can present

    typical organ involvement
    SYMPTOMS

 and, thus, have to be treated respectively. This synopsis wants to systematically review the typical

    organ involvement
    SYMPTOMS

 in

    female
    GENDER

    Fabry
    DIAGNOSIS

 patients. Moreover, therapy recommendations especially for

    female
    GENDER

 patients are discussed.

Fabry's disease
rare genetic storage disorder
Fabry

typical organ involvement
organ involvement


Case report: Long-term outcome post-heart transplantation in a woman with Fabry's disease.

Fabry's disease is an X-linked recessive disorder that results from the deficiency of alpha-galactosidase A and causes the accumulation of globotriaosylceramide (Gb3) in different tissues. It leads to a rare form of cardiomyopathy which may be complicated by end-stage heart failure and need to heart transplant. Our group described the first case of heart transplant in a woman with cardiomyopathy secondary to Fabry's disease about 12 years ago. There was uncertainty in regards to the possibility of recurrence of the disease as previously documented in kidney transplant recipients and long-term outcomes. In this report, 14 years after transplant, this woman is still alive and there is no evidence of Fabry's disease in any of the endomyocardial biopsies. Heart transplantation can be recommended for Fabry's patients with end-stage cardiomyopathy.

    Fabry's disease
    DIAGNOSIS

 is an

    X-linked recessive disorder
    GENETICS

 that results from the

    deficiency of alpha-galactosidase A
    BIOCHEMICAL

 and causes the

    accumulation of globotriaosylceramide (Gb3) in different tissues
    MICROSCOPIC

. It leads to a rare form of

    cardiomyopathy
    DIAGNOSIS

 which may be complicated by

    end-stage heart failure
    SYMPTOMS

 and need to

    heart transplant
    MEDICATION

. Our group described the first case of

    heart transplant
    MEDICATION

 in a

    woman
    GENDER

 with

    cardiomyopathy
    DIAGNOSIS

 secondary to

    Fabry's disease
    DIAGNOSIS

 about 12 years ago. There was uncertainty in regards to the possibility of recurrence of the disease as previously documented in

    kidney transplant
    MEDICATION

 recipients and long-term outcomes. In this report, 14 years after

    transplant
    MEDICATION

, this

    woman
    GENDER

 is still alive and there is

    no evidence of Fabry's disease in any of the endomyocardial biopsies
    NEG_FINDINGS

.

    Heart transplantation
    MEDICATION

 can be recommended for

    Fabry's
    DIAGNOSIS

 patients with

    end-stage cardiomyopathy
    DIAGNOSIS

.

Fabry's disease
cardiomyopathy
cardiomyopathy
Fabry's disease
Fabry's
end-stage cardiomyopathy

heart transplant
heart transplant
kidney transplant
transplant
Heart transplantation


Early diagnosis of fabry disease in a patient with toe tip pain.

Fabry disease is an X-linked lysosomal disease caused by deficiency of α-galactosidase, in which early diagnosis may be missed due to the wide variety of clinical symptoms presenting during disease progression. A 13 year-old boy visited our pain clinic complaining of pricking and burning pain in the toe tips of both feet. Continuous epidural infusion for pain management was performed because of oral analgesics ineffectiveness. The patient underwent α-galactosidase A (GLA) enzyme analysis based on the clinical impression of Fabry disease from pain with a peripheral neuropathic component and history of anhidrosis. He was diagnosed with Fabry disease after confirming mutation of the GLA gene through a screening test of GLA activity. Enzyme replacement therapy was initiated and pain was tolerated with oral analgesics.

    Fabry disease
    DIAGNOSIS

 is an

    X-linked
    GENETICS

    lysosomal disease
    DIAGNOSIS

 caused by

    deficiency of α-galactosidase
    BIOCHEMICAL

, in which early diagnosis may be missed due to the wide variety of clinical symptoms presenting during disease progression. A

    13 year-old
    AGE

    boy
    GENDER

 visited our pain clinic complaining of

    pricking and burning pain in the toe tips of both feet
    SYMPTOMS

.

    Continuous epidural infusion for pain management
    MEDICATION

 was performed because of

    oral analgesics ineffectiveness
    NEG_FINDINGS

. The patient underwent

    α-galactosidase A (GLA) enzyme analysis
    PARACLINICAL

 based on the clinical impression of

    Fabry disease
    DIAGNOSIS

 from

    pain with a peripheral neuropathic component
    SYMPTOMS

 and

    history of anhidrosis
    SYMPTOMS

.

    He
    GENDER

 was diagnosed with

    Fabry disease
    DIAGNOSIS

 after confirming

    mutation of the GLA gene
    GENETICS

 through a

    screening test of GLA activity
    PARACLINICAL

.

    Enzyme replacement therapy
    MEDICATION

 was initiated and

    pain was tolerated with oral analgesics
    NEG_FINDINGS

.

Fabry disease
lysosomal disease
Fabry disease
Fabry disease

oral analgesics ineffectiveness
pain was tolerated with oral analgesics


Cardiac magnetic resonance imaging in patients with Fabry's disease.

Fabry's disease (FD) is a rare hereditary disorder caused by the loss of alpha galactosidase A activity leading to accumulation of glycosphingolipids in various organs including hypertrophy of the heart. Most reports on cardiac involvement in FD focus on the left ventricular hypertrophy (LVH) and its relation to diastolic function. However, recent studies demonstrated large subset of patients with FD and right ventricle (RV) hypertophy. The accurate depiction of RV volumes, function and mass is possible with cardiovascular magnetic resonance (CMR). The CMR study can be also used to identify typically localised regions of intramyocardial fibrosis (infero-lateral segments of the LV), which have been shown to be a marker of inefficacious response to enzyme replacement therapy. We present series of 8 patients with genetically confirmed FD who underwent CMR study. We demonstrated a typical concentric and diffuse pattern of LVH with RV involvement in patients with the most severe LVH without significant impact on RV function and volumes. We showed that myocardial fibrosis can be observed not only in LV but also in RV. In 2 patients FD coexisted with symptomatic coronary artery disease with evidence of subendocardial myocardial fibrosis typical for ischaemic origin in one patient. The CMR confirmation of the presence of FD in one patient at an early stage of the disease, before the onset of advanced hypertrophy or failure of other organs, supports the value of this imaging technique in differential diagnosis of concentric and diffuse LVH.

    Fabry's disease (FD)
    DIAGNOSIS

 is a

    rare hereditary disorder
    GENETICS

 caused by the

    loss of alpha galactosidase A activity
    BIOCHEMICAL

 leading to

    accumulation of glycosphingolipids in various organs
    MICROSCOPIC

 including

    hypertrophy of the heart
    MICROSCOPIC

. Most reports on

    cardiac involvement
    SYMPTOMS

 in

    FD
    DIAGNOSIS

 focus on the

    left ventricular hypertrophy (LVH)
    SYMPTOMS

 and its relation to

    diastolic function
    SYMPTOMS

. However, recent studies demonstrated large subset of patients with

    FD
    DIAGNOSIS

 and

    right ventricle (RV) hypertophy
    SYMPTOMS

. The accurate depiction

    of RV volumes, function and mass
    PARACLINICAL

 is possible with

    cardiovascular magnetic resonance (CMR)
    PARACLINICAL

. The

    CMR study
    PARACLINICAL

 can be also used to identify

    typically localised regions of intramyocardial fibrosis (infero-lateral segments of the LV)
    SYMPTOMS

, which have been shown to be a marker of

    inefficacious response to enzyme replacement therapy
    NEG_FINDINGS

. We present series of 8 patients with genetically confirmed

    FD
    DIAGNOSIS

 who underwent

    CMR study
    PARACLINICAL

. We demonstrated a

    typical concentric and diffuse pattern of LVH with RV involvement
    SYMPTOMS

 in patients with the

    most severe LVH
    SYMPTOMS

    without significant impact on RV function and volumes
    NEG_FINDINGS

. We showed that

    myocardial fibrosis can be observed not only in LV but also in RV
    SYMPTOMS

. In 2 patients

    FD
    DIAGNOSIS

 coexisted with

    symptomatic coronary artery disease
    SYMPTOMS

 with

    evidence of subendocardial myocardial fibrosis typical for ischaemic origin
    SYMPTOMS

 in one patient. The

    CMR
    PARACLINICAL

 confirmation of the presence of

    FD
    DIAGNOSIS

 in one patient at an early stage of the disease, before the onset of

    advanced hypertrophy or failure of other organs
    SYMPTOMS

, supports the value of this imaging technique in

    differential diagnosis
    PARACLINICAL

 of

    concentric and diffuse LVH
    DIAGNOSIS

.

Fabry's disease (FD)
FD
FD
FD
FD
FD
concentric and diffuse LVH