Vasospastic angina in a patient with Fabry's disease who showed normal coronary angiographic findings.

It has been reported that coronary diseases in patients with Fabry's disease are induced by deposits in endothelial cells and coronary smooth muscle cells. Most of those are ischemia due to stenosis. This report describes a case of patient with Fabry's disease who showed severe vasospasms without coronary artery stenosis during acetylcholine loaded coronary angiography. In this case, a myocardial biopsy revealed that the deposits in the endothelial cells of the myocardial capillaries were lamellated appearance. Recently, it is reported that endothelial cell damage could be an important cause of coronary vasospasm. This case suggests that the some sort of functional disorder was induced by glyco-sphingolipid deposits in the coronary endothelial cells, and that this might have led to coronary artery spasms without the organic stenosis of coronary arteries.

It has been reported that

    coronary diseases
    SYMPTOMS

 in patients with

    Fabry's disease
    DIAGNOSIS

 are induced by

    deposits in endothelial cells and coronary smooth muscle cells
    MICROSCOPIC

. Most of those are

    ischemia due to stenosis
    SYMPTOMS

. This report describes a case of patient with

    Fabry's disease
    DIAGNOSIS

 who showed

    severe vasospasms
    SYMPTOMS

    without coronary artery stenosis
    NEG_FINDINGS

 during

    acetylcholine loaded coronary angiography
    PARACLINICAL

. In this case, a

    myocardial biopsy
    PARACLINICAL

 revealed that

    the deposits in the endothelial cells of the myocardial capillaries were lamellated appearance
    MICROSCOPIC

. Recently, it is reported that

    endothelial cell damage
    SYMPTOMS

 could be an important cause of

    coronary vasospasm
    SYMPTOMS

. This case suggests that the some sort of functional disorder was induced by

    glyco-sphingolipid deposits in the coronary endothelial cells
    MICROSCOPIC

, and that this might have led to

    coronary artery spasms
    SYMPTOMS

    without the organic stenosis of coronary arteries
    NEG_FINDINGS

.

coronary diseases
ischemia due to stenosis
severe vasospasms
endothelial cell damage
coronary vasospasm
coronary artery spasms


Novel trinucleotide deletion in Fabry's disease.

We describe the molecular characterization of a novel, in-frame deletion that is located in exon 7 of the alpha-galactosidase A gene in a patient with Fabry's disease. The 3-bp deletion we identified, besides the typical severe clinical features, also expresses diffuse facial telangiectasias, which is a new cutaneous marker of Fabry's disease.

We describe the molecular characterization of a

    novel, in-frame deletion that is located in exon 7 of the alpha-galactosidase A gene
    GENETICS

 in a patient with

    Fabry's disease
    DIAGNOSIS

. The

    3-bp deletion
    GENETICS

 we identified, besides the typical

    severe clinical features
    SYMPTOMS

, also expresses

    diffuse facial telangiectasias
    SYMPTOMS

, which is a new cutaneous marker of

    Fabry's disease
    DIAGNOSIS

.

severe clinical features
diffuse facial telangiectasias


Possible mechanism of anhidrosis in a symptomatic female carrier of Fabry's disease: an assessment by skin sympathetic nerve activity and sympathetic skin response.

Fabry's disease, X-linked alpha-galactosidase deficiency, features a variety of autonomic abnormalities including anhidrosis. In this study, we measured the skin sympathetic nerve activity (SSNA), skin potential and sweat rate in a symptomatic female carrier to investigate the underlying pathophysiology of anhidrosis. The basal activity and responsiveness of SSNA were both fairly well preserved, although slightly reduced compared with the control levels. However, sweating was completely absent, despite the normal skin potential change in response to SSNA bursts. These results suggest that anhidrosis in Fabry's disease is a result of sweat gland dysfunction as well as abnormal SSNA.

    Fabry's disease
    DIAGNOSIS

,

    X-linked
    GENETICS

    alpha-galactosidase deficiency
    BIOCHEMICAL

, features a variety of

    autonomic abnormalities
    SYMPTOMS

 including

    anhidrosis
    SYMPTOMS

. In this study, we

    measured the skin sympathetic nerve activity (SSNA), skin potential and sweat rate
    PARACLINICAL

 in a symptomatic

    female
    GENDER

 carrier to investigate the underlying pathophysiology of

    anhidrosis
    DIAGNOSIS

. The

    basal activity and responsiveness of SSNA were both fairly well preserved, although slightly reduced compared with the control levels
    NEG_FINDINGS

. However,

    sweating was completely absent
    NEG_FINDINGS

,

    despite the normal skin potential change in response to SSNA bursts
    NEG_FINDINGS

. These results suggest that

    anhidrosis
    SYMPTOMS

 in

    Fabry's disease
    DIAGNOSIS

 is a result of

    sweat gland dysfunction
    SYMPTOMS

 as well as

    abnormal SSNA
    BIOCHEMICAL

.

Fabry's disease
anhidrosis
Fabry's disease

alpha-galactosidase deficiency
abnormal SSNA

autonomic abnormalities
anhidrosis
anhidrosis
sweat gland dysfunction


The Ilizarov external fixator for treatment of deformities in Paget's disease.

Paget's disease of bone may cause progressive bowing of affected femurs and tibiae. Fractures or osteotomies in these patients technically are difficult to treat and may lead to delayed union or nonunion. The authors report their early results with the use of the Ilizarov external fixator to affix 3 corrective closing wedge osteotomies, 1 fracture, and 1 delayed union. Deformities were corrected fully during the surgery, with an option to correct remaining deformation progressively during the rest of treatment. Compression of the healing bone was applied to enhance osseous healing, when necessary. Three-dimensional control is possible, and the stability of the fixation is excellent in this structurally weak bone. Bony union was achieved without complications in all patients within 4 months.

    Paget's disease of bone
    DIAGNOSIS

 may cause

    progressive bowing of affected femurs and tibiae
    SYMPTOMS

.

    Fractures or osteotomies
    MEDICATION

 in these patients technically are difficult to treat and may lead to

    delayed union
    SYMPTOMS

 or

    nonunion
    SYMPTOMS

. The authors report their early results with the use of the

    Ilizarov external fixator
    MEDICATION

 to

    affix
    MEDICATION

 3

    corrective closing wedge osteotomies
    MEDICATION

, 1

    fracture
    DIAGNOSIS

, and 1

    delayed union
    SYMPTOMS

.

    Deformities were corrected fully during the surgery
    SYMPTOMS

, with an option to correct remaining deformation progressively during the rest of treatment.

    Compression of the healing bone
    MEDICATION

 was applied to

    enhance osseous healing
    MEDICATION

, when necessary.

    Three-dimensional control
    PARACLINICAL

 is possible, and the

    stability of the fixation is excellent
    SYMPTOMS

 in this

    structurally weak bone
    SYMPTOMS

.

    Bony union
    SYMPTOMS

 was achieved

    without complications
    NEG_FINDINGS

 in all patients within 4 months.

Fractures or osteotomies
Ilizarov external fixator
affix
corrective closing wedge osteotomies
Compression of the healing bone
enhance osseous healing


Galactosialidosis in two siblings.

Galactosialidosis is a rare lysosomal storage disease associated with deficiencies of alpha-galactosidase and beta-neurominidase. In this report, two siblings with galactosialidosis, resembling Niemann-Pick disease with the presence of foamy cells in multiple organs, splenomegaly and prominent hepatomegaly, are presented. Galactosidase deficiency and an increased number of urinary sialic acid compounds were determined in these cases, and prenatal diagnosis was performed for their fourth sibling. Besides the presence of the typical clinical features, enzyme study is essential for the diagnosis of lysosomal storage disease and it facilitates in making the prenatal diagnosis.

    Galactosialidosis
    DIAGNOSIS

 is a

    rare lysosomal storage disease
    DIAGNOSIS

 associated with

    deficiencies of alpha-galactosidase and beta-neurominidase
    BIOCHEMICAL

. In this report, two siblings with

    galactosialidosis
    DIAGNOSIS

, resembling

    Niemann-Pick disease
    MICROSCOPIC

 with the

    presence of foamy cells in multiple organs
    MICROSCOPIC

,

    splenomegaly
    SYMPTOMS

 and

    prominent hepatomegaly
    SYMPTOMS

, are presented.

    Galactosidase deficiency
    BIOCHEMICAL

 and an

    increased number of urinary sialic acid compounds
    MICROSCOPIC

 were determined in these cases, and

    prenatal diagnosis
    MEDICATION

 was performed for

    their fourth sibling
    FAMILY

. Besides the presence of the typical clinical features,

    enzyme study
    PARACLINICAL

 is essential for the diagnosis of

    lysosomal storage disease
    DIAGNOSIS

 and it facilitates in making the prenatal diagnosis.

Galactosialidosis
rare lysosomal storage disease
galactosialidosis
lysosomal storage disease


Novel frameshift mutation in a heterozygous woman with Fabry disease and end-stage renal failure.

It is generally accepted that Fabry disease (angiokeratoma corporis diffusum) is an X-linked disorder resulting from the deficient activity of the lysosomal enzyme alpha-galactosidase. In males, the enzymatic defect leads to accumulation of glycosphingolipids, particularly in the kidney which causes end-stage renal disease. We report here a woman who presented in 1987 with focal and segmental glomerulosclerosis and required hemodialysis 4 years later when her son was evaluated for proteinuria. In these patients morphologic, biochemical, and genetic investigations were performed to explore the possibility of a hereditary renal disorder. Ultrastructural examination of the son's renal biopsy specimen revealed lamellated osmiophilic inclusions in the glomeruli, typical of Fabry disease. Four months after kidney transplantation in the mother, a graft biopsy specimen also revealed dense lamellated inclusions on electron microscopy. The leukocyte alpha-galactosidase activity was 0.008 mumol/min.10(9) cells in the son and 0.070 in the mother (range 0.100-0.500 mumol/min.10(9) cells). The diagnosis of Fabry disease was confirmed in both patients by the identification by DNA sequencing of a novel mutation in the alpha-galactosidase gene: one single base pair deletion in exon 3 (7317delA).

(1) end-stage renal disease may occur in heterozygous women with Fabry disease; (2) morphologic lesions due to glycosphingolipid accumulation may be observed in the renal allograft after transplantation, and (3) DNA analysis confirmed the diagnosis by demonstrating a frameshift mutation, which has as yet not been reported.

It is generally accepted that

    Fabry disease
    DIAGNOSIS

 (

    angiokeratoma corporis diffusum
    SYMPTOMS

    )
    DIAGNOSIS

 is an

    X-linked disorder
    GENETICS

 resulting from the

    deficient activity of the lysosomal enzyme alpha-galactosidase
    BIOCHEMICAL

. In

    males
    GENDER

, the

    enzymatic defect
    BIOCHEMICAL

 leads to

    accumulation of glycosphingolipids, particularly in the kidney
    MICROSCOPIC

 which causes

    end-stage renal disease
    DIAGNOSIS

. We report here a

    woman
    GENDER

 who presented in 1987 with

    focal and segmental glomerulosclerosis
    DIAGNOSIS

 and required

    hemodialysis
    MEDICATION

 4 years later when

    her
    GENDER

    son
    FAMILY

 was evaluated for

    proteinuria
    BIOCHEMICAL

. In these patients

    morphologic, biochemical, and genetic investigations
    PARACLINICAL

 were performed to explore the possibility of a

    hereditary renal disorder
    DIAGNOSIS

.

    Ultrastructural examination of the son's renal biopsy specimen
    PARACLINICAL

 revealed

    lamellated osmiophilic inclusions in the glomeruli, typical of Fabry disease
    MICROSCOPIC

. Four months after

    kidney transplantation in the mother
    MEDICATION

, a

    graft biopsy specimen
    PARACLINICAL

 also revealed

    dense lamellated inclusions
    MICROSCOPIC

 on

    electron microscopy
    PARACLINICAL

.

    The leukocyte alpha-galactosidase activity was 0.008 mumol/min.10(9) cells in the son and 0.070 in the mother (range 0.100-0.500 mumol/min.10(9) cells)
    BIOCHEMICAL

. The diagnosis of

    Fabry disease
    DIAGNOSIS

 was confirmed in both patients by the identification by

    DNA sequencing
    PARACLINICAL

 of a novel mutation in the alpha-galactosidase gene: one single base pair deletion in exon 3 (7317delA).

(1)

    end-stage renal disease
    DIAGNOSIS

 may occur in

    heterozygous
    GENETICS

    women
    GENDER

 with

    Fabry disease
    DIAGNOSIS

; (2)

    morphologic lesions due to glycosphingolipid accumulation may be observed in the renal allograft
    MICROSCOPIC

 after

    transplantation
    MEDICATION

, and (3)

    DNA analysis
    PARACLINICAL

 confirmed the diagnosis by demonstrating a

    frameshift mutation
    GENETICS

, which has as yet not been reported.

Fabry disease
)
end-stage renal disease
focal and segmental glomerulosclerosis
hereditary renal disorder
Fabry disease
end-stage renal disease
Fabry disease

X-linked disorder
heterozygous
frameshift mutation

hemodialysis
kidney transplantation in the mother
transplantation


Atypical Fabry's disease. An oligosymptomatic variant.

Fabry's disease is a rare, inherited, X-linked metabolic storage disease with ceramide hexoside due to alpha-galactosidase A deficiency. Patients with typical Fabry's disease usually present with several clinical manifestations of corneal dystrophy, neurologic abnormalities, cardiovascular disease, heavy proteinuria, and characteristic cutaneous angiokeratoma. However, atypical Fabry's disease with oligosymptomatic phenotype presents with symptoms restricted solely to cardiocytes or kidney and might be diagnosed by chance during a routine endomyocardial or renal biopsy examination. In this article, we report a case of Fabry's disease incidentally diagnosed in a 34-year-old man who presented with intermittent trace or 1(+) proteinuria only. This patient had no history of renal disease in any other family member. A renal biopsy to evaluate trace proteinuria revealed histologic and ultrastructural findings compatible with Fabry's disease. Subsequent to the renal biopsy, a skin biopsy on a few initially unrecognized, scattered, dark-pinkish scrotal papules showed typical angiokeratoma. A biochemical enzymatic assay of alpha-galactosidase in urine and plasma revealed a markedly decreased enzyme level in the hemizygous range.

    Fabry's disease
    DIAGNOSIS

 is a

    rare, inherited
    GENETICS

,

    X-linked
    GENETICS

    metabolic storage disease
    DIAGNOSIS

 with

    ceramide hexoside
    MICROSCOPIC

 due to

    alpha-galactosidase A deficiency
    BIOCHEMICAL

. Patients with typical

    Fabry's disease
    DIAGNOSIS

 usually present with several clinical manifestations of

    corneal dystrophy
    SYMPTOMS

,

    neurologic abnormalities
    SYMPTOMS

,

    cardiovascular disease
    SYMPTOMS

,

    heavy proteinuria
    BIOCHEMICAL

, and

    characteristic cutaneous angiokeratoma
    SYMPTOMS

. However,

    atypical Fabry's disease
    DIAGNOSIS

 with

    oligosymptomatic phenotype
    SYMPTOMS

 presents with

    symptoms restricted solely to cardiocytes or kidney
    SYMPTOMS

 and might be diagnosed by chance during a routine

    endomyocardial or renal biopsy examination
    PARACLINICAL

. In this article, we report a case of

    Fabry's disease
    DIAGNOSIS

 incidentally diagnosed in a

    34-year-old
    AGE

    man
    GENDER

 who presented with

    intermittent trace or 1(+) proteinuria only
    BIOCHEMICAL

. This patient had

    no history of renal disease in any other family member
    NEG_FINDINGS

. A

    renal biopsy
    PARACLINICAL

 to evaluate

    trace proteinuria
    BIOCHEMICAL

 revealed

    histologic and ultrastructural findings
    SYMPTOMS

 compatible with

    Fabry's disease
    DIAGNOSIS

. Subsequent to the

    renal biopsy
    PARACLINICAL

, a

    skin biopsy
    PARACLINICAL

 on a few

    initially unrecognized, scattered, dark-pinkish scrotal papules
    SYMPTOMS

 showed

    typical angiokeratoma
    SYMPTOMS

. A

    biochemical enzymatic assay of alpha-galactosidase in urine and plasma
    PARACLINICAL

 revealed a

    markedly decreased enzyme level in the hemizygous range
    BIOCHEMICAL

.

Fabry's disease
metabolic storage disease
Fabry's disease
atypical Fabry's disease
Fabry's disease
Fabry's disease


A female heterozygous patient with Fabry's disease with renal accumulation of trihexosylceramide detected with a monoclonal antibody.

We describe a female patient with heterozygous Fabry's disease. The patient had persistent proteinuria and microhematuria but lacked any other diagnostic signs such as corneal and cutaneous involvement. Kidney tissue obtained at biopsy showed the segmentally distributed enlarged glomerular epithelia. These cells were filled with vacuolated foamy cytoplasm, which had lamellar and myelinoid structures under electronmicroscopic observation. Accumulation of trihexosylceramide (CTH) in these foamy epithelial cells was confirmed with immunohistochemical staining with the use of anti-CTH monoclonal antibody. Alpha-galactosidase activity of leukocytes was 67 nmol/mg protein/hr, which was approximately half that of the normal population (mean +/- SD, 147 +/- 65 nmol/mg protein/hr, n = 20). All of these findings were compatible with the diagnosis of heterozygous Fabry's disease. We recommend that kidney tissue biopsy specimens suggesting Fabry's disease be immunostained with anti-CTH antibody.

We describe a

    female
    GENDER

 patient with

    heterozygous Fabry's disease
    DIAGNOSIS

. The patient had

    persistent proteinuria
    BIOCHEMICAL

 and

    microhematuria
    BIOCHEMICAL

 but

    lacked any other diagnostic signs such as corneal and cutaneous involvement
    NEG_FINDINGS

.

    Kidney tissue
    PARACLINICAL

 obtained at

    biopsy
    PARACLINICAL

 showed

    the segmentally distributed enlarged glomerular epithelia
    MICROSCOPIC

.

    These cells were filled with vacuolated foamy cytoplasm, which had lamellar and myelinoid structures
    MICROSCOPIC

 under

    electronmicroscopic observation
    PARACLINICAL

.

    Accumulation of trihexosylceramide (CTH) in these foamy epithelial cells
    MICROSCOPIC

 was confirmed with

    immunohistochemical staining
    PARACLINICAL

 with the use of anti-CTH monoclonal antibody.

    Alpha-galactosidase activity of leukocytes was 67 nmol/mg protein/hr, which was approximately half that of the normal population (mean +/- SD, 147 +/- 65 nmol/mg protein/hr
    BIOCHEMICAL

, n = 20). All of these findings were compatible with the diagnosis of

    heterozygous Fabry's disease
    DIAGNOSIS

. We recommend that

    kidney tissue biopsy specimens
    PARACLINICAL

 suggesting

    Fabry's disease
    DIAGNOSIS

 be

    immunostained with anti-CTH antibody
    PARACLINICAL

.

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


[Angiokeratoma corporis diffusum without associated metabolic disorder].

In a 22-year-old woman with mental impairment and some signs of dysmorphism, numerous angiokeratomas developed, starting when she was 3 years old and resulting in the clinical picture of angiokeratoma corporis diffusum. Extensive laboratory analyses did not disclose any associated metabolic disorder,and electron microscopy failed to demonstrate lysosomal inclusions. Therefore, this patient can be classified as one of the rare cases of angiokeratoma corporis diffusum without associated metabolic disease (idiopathic angiokeratoma corporis diffusum).

In a

    22-year-old
    AGE

    woman
    GENDER

 with

    mental impairment
    SYMPTOMS

 and

    some signs of dysmorphism
    SYMPTOMS

,

    numerous angiokeratomas
    SYMPTOMS

 developed, starting when

    she
    GENDER

    was 3 years old
    AGE

 and resulting in the clinical picture of

    angiokeratoma corporis diffusum
    SYMPTOMS

.

    Extensive laboratory analyses
    PARACLINICAL

    did not disclose any associated metabolic disorder
    NEG_FINDINGS

,and

    electron microscopy
    PARACLINICAL

    failed to demonstrate lysosomal inclusions
    NEG_FINDINGS

. Therefore, this patient can be classified as one of the rare cases of

    angiokeratoma corporis diffusum
    SYMPTOMS

    without associated metabolic disease
    NEG_FINDINGS

 (

    idiopathic angiokeratoma corporis diffusum)
    DIAGNOSIS

.

mental impairment
some signs of dysmorphism
numerous angiokeratomas
angiokeratoma corporis diffusum
angiokeratoma corporis diffusum


A case of Fabry's disease with granulomatous interstitial nephritis.

A 15-year-old boy with proteinuria and hematuria is reviewed in this study. He was first found to have urinary abnormalities at the age of 13 years, and his renal function was exacerbated for a short duration. Renal biopsy was performed to make a histological diagnosis and to establish adequate therapy. Light microscopy showed marked tubulointerstitial inflammation with granulomatous changes, and electron microscopy revealed that numerous osmiophilic inclusions were present in podocytes, mesangial cells, and endothelial cells of the glomeruli and in epithelial cells of the tubules. The alpha-galactosidase activity of lymphocytes from the patient was measured, and the results of this assay indicated that the patient's lymphocytes had a low level of alpha-galactosidase activity. Therefore, the patient was diagnosed as having Fabry's disease with renal dysfunction. This study demonstrated that the onset age of renal insufficiency in Fabry's disease may be earlier than that described previously, and that when granulomatous interstitial nephritis is developed, renal function may deteriorate progressively.

A

    15-year-old
    AGE

    boy
    GENDER

 with

    proteinuria
    BIOCHEMICAL

 and

    hematuria
    BIOCHEMICAL

 is reviewed in this study.

    He
    GENDER

 was first found to have

    urinary abnormalities
    SYMPTOMS

 at the

    age of 13 years
    AGE

, and his

    renal function was exacerbated for a short duration
    SYMPTOMS

.

    Renal biopsy
    PARACLINICAL

 was performed to make a

    histological diagnosis
    PARACLINICAL

 and to establish adequate therapy.

    Light microscopy
    PARACLINICAL

 showed

    marked tubulointerstitial inflammation with granulomatous changes
    MICROSCOPIC

, and

    electron microscopy
    PARACLINICAL

 revealed that

    numerous osmiophilic inclusions were present in podocytes, mesangial cells, and endothelial cells of the glomeruli and in epithelial cells of the tubules
    MICROSCOPIC

.

    The alpha-galactosidase activity of lymphocytes from the patient was measured
    BIOCHEMICAL

, and the results of this assay indicated that the patient's

    lymphocytes had a low level of alpha-galactosidase activity
    BIOCHEMICAL

. Therefore, the patient was diagnosed as having

    Fabry's disease
    DIAGNOSIS

 with

    renal dysfunction
    SYMPTOMS

. This study demonstrated that the onset age of

    renal insufficiency
    SYMPTOMS

 in

    Fabry's disease
    DIAGNOSIS

 may be earlier than that described previously, and that when

    granulomatous interstitial nephritis
    DIAGNOSIS

 is developed,

    renal function
    SYMPTOMS

 may

    deteriorate
    SYMPTOMS

 progressively.

Fabry's disease
Fabry's disease
granulomatous interstitial nephritis


[The anesthetic management of a patient with Fabry's disease].

There are no reports of anesthesia for a patient with Fabry's Disease in Japan. Fabry's Disease is a rare hereditary disease that is characterized by alpha-galactosidase deficiency caused by deposition of glycolipid in many organs. The disease may be complicated by cardiac ischemic disease, neurological disorder and renal failure. The patient is a 45-year-old female with cholelithiasis who underwent cholecystectomy. This patient had been hospitalized repeatedly for the past 15 years because of the chronic pyelits, and hyperglycemia, and nephrosis. She developed chronic renal failure, hemodialysis was started when diagnosis of Fabry's Disease was made at age of 41. Preoperative electrocardiogram revealed ischemic change on leads II, V5 and V6. Nifedipine was administered for hypertension. The anesthesia was induced with thiopental followed by vecuronium for endotracheal intubation, and maintained with nitrous oxide, oxygen and isoflurane. Accompanied by nicardipine for hypertension, and vecuronium for muscle relaxation using a neurotransmission monitor (Relaxograph), nitroglycerin was continuously infused. We avoided the effect of atropine for reversal of muscle relaxation because most of the patients were complicated with hypohidrosis. During administration of nitroglycerin and nicardipine, the neuromuscular blocking effects of vecuronium could be prolonged. The neuromuscular monitoring was useful in this case.

There are no reports of

    anesthesia
    MEDICATION

 for a patient with

    Fabry's Disease
    DIAGNOSIS

 in

    Japan
    ETHNICITY

.

    Fabry's Disease
    DIAGNOSIS

 is a

    rare hereditary disease
    GENETICS

 that is characterized by

    alpha-galactosidase deficiency
    BIOCHEMICAL

 caused by

    deposition of glycolipid in many organs
    MICROSCOPIC

. The disease may be complicated by

    cardiac ischemic disease
    SYMPTOMS

,

    neurological disorder
    SYMPTOMS

 and

    renal failure
    SYMPTOMS

. The patient is a

    45-year-old
    AGE

    female
    GENDER

 with

    cholelithiasis
    DIAGNOSIS

 who underwent

    cholecystectomy
    MEDICATION

. This patient had been hospitalized repeatedly for the past 15 years because of the

    chronic pyelits
    DIAGNOSIS

, and

    hyperglycemia
    SYMPTOMS

, and

    nephrosis
    DIAGNOSIS

.

    She
    GENDER

 developed

    chronic renal failure
    SYMPTOMS

,

    hemodialysis
    MEDICATION

 was started when diagnosis of

    Fabry's Disease
    DIAGNOSIS

 was made at

    age of 41
    AGE

. Preoperative

    electrocardiogram
    PARACLINICAL

 revealed

    ischemic change on leads II, V5 and V6
    SYMPTOMS

.

    Nifedipine
    MEDICATION

 was administered for

    hypertension
    SYMPTOMS

. The

    anesthesia
    MEDICATION

 was

    induced with thiopental followed by vecuronium for endotracheal intubation
    MEDICATION

, and

    maintained with nitrous oxide, oxygen and isoflurane
    MEDICATION

. Accompanied by

    nicardipine
    MEDICATION

 for

    hypertension
    MEDICATION

, and

    vecuronium for muscle relaxation
    MEDICATION

 using a

    neurotransmission monitor (Relaxograph)
    PARACLINICAL

,

    nitroglycerin was continuously infused
    MEDICATION

. We

    avoided the effect of atropine for reversal of muscle relaxation
    NEG_FINDINGS

 because most of the patients were complicated with

    hypohidrosis
    SYMPTOMS

. During

    administration of nitroglycerin and nicardipine
    MEDICATION

, the

    neuromuscular blocking effects of vecuronium could be prolonged
    SYMPTOMS

. The

    neuromuscular monitoring
    PARACLINICAL

 was useful in this case.

Fabry's Disease
Fabry's Disease
cholelithiasis
chronic pyelits
nephrosis
Fabry's Disease


Headache associated with aseptic meningeal reaction as clinical onset of Fabry's disease.

This report concerns an 18-year-old boy who is hemizygote for Fabry's disease. Varying degrees of nonpulsating headache crises, lasting from a few hours to several days, began when he was 16 years of age. Painful crises in the extremities, characteristic of Fabry's disease, were not present. Although only occasional, he had several episodes of throbbing headache with vomiting without aura. The meningeal signs were equivocal, although the patient had noninfectious pleocytosis, intracranial hypertension, delayed radioisotope clearance on cisternography, and multiple old cerebral infarcts. Nonsteroidal anti-inflammatory drugs, antidepressants, carbamazepine, and glycerol were of no benefit for his headache. Although its mode of action remains obscure, prednisolone was effective for treating the headache and the aseptic meningeal reaction.

This report concerns an

    18-year-old
    AGE

    boy
    GENDER

 who is

    hemizygote for Fabry's disease
    GENETICS

.

    Varying degrees of nonpulsating headache crises, lasting from a few hours to several days
    SYMPTOMS

, began when

    he
    GENDER

 was

    16 years of age
    AGE

.

    Painful crises in the extremities
    SYMPTOMS

, characteristic of

    Fabry's disease
    SYMPTOMS

, were

    not present
    NEG_FINDINGS

. Although only occasional,

    he
    GENDER

 had

    several episodes of throbbing headache with vomiting
    SYMPTOMS

    without aura
    NEG_FINDINGS

.

    The meningeal signs were equivocal
    NEG_FINDINGS

, although the patient had

    noninfectious pleocytosis
    BIOCHEMICAL

,

    intracranial hypertension
    SYMPTOMS

,

    delayed radioisotope clearance on cisternography
    SYMPTOMS

, and

    multiple old cerebral infarcts
    SYMPTOMS

.

    Nonsteroidal anti-inflammatory drugs, antidepressants, carbamazepine, and glycerol were of no benefit for his headache
    NEG_FINDINGS

. Although its mode of action remains obscure,

    prednisolone
    MEDICATION

 was effective for treating the

    headache
    SYMPTOMS

 and the

    aseptic meningeal reaction
    SYMPTOMS

.


Painful fingers, heat intolerance, and telangiectases of the ear: easily ignored childhood signs of Fabry disease.

Generalized anhidrosis with heat collapse, painful fingers, and angiokeratomas were the presenting signs in a 23-year-old man who was shown by enzyme studies and electron microscopy to have Fabry disease. His 6-year-old brother had the early diagnostic findings of episodic painful fingers, heat intolerance, and retroauricular telangiectasia. Both had an absence of alpha-galactosidase. Over 6 years of observation, the older brother developed progressive renal failure and the younger one developed acrodynia and anhidrosis. Their mother had diminished alpha-galactosidase activity and several angiomatous papules on one breast. A review of Fabry disease emphasizes the need for skin inspection for angiomas and telangiectasia, and enzyme assay in patients with inexplicable complaints or findings. Carrier females are most easily recognized by the presence of unique corneal opacities.

    Generalized anhidrosis with heat collapse
    SYMPTOMS

,

    painful fingers
    SYMPTOMS

, and

    angiokeratomas
    SYMPTOMS

 were the presenting signs in a

    23-year-old
    AGE

    man
    GENDER

 who was shown by

    enzyme studies
    PARACLINICAL

 and

    electron microscopy
    PARACLINICAL

 to have

    Fabry disease
    DIAGNOSIS

.

    His
    GENDER

    6-year-old
    AGE

    brother
    GENDER

 had the early diagnostic findings of

    episodic painful fingers
    SYMPTOMS

,

    heat intolerance
    SYMPTOMS

, and

    retroauricular telangiectasia
    SYMPTOMS

.

    Both
    GENDER

 had an

    absence of alpha-galactosidase
    BIOCHEMICAL

. Over 6 years of observation, the

    older brother
    AGE

 developed

    progressive renal failure
    SYMPTOMS

 and the younger one developed

    acrodynia
    SYMPTOMS

 and

    anhidrosis
    SYMPTOMS

. Their

    mother had diminished alpha-galactosidase activity
    FAMILY

 and

    several angiomatous papules on one breast
    SYMPTOMS

. A review of

    Fabry disease
    DIAGNOSIS

 emphasizes the need for

    skin inspection
    PARACLINICAL

 for

    angiomas
    SYMPTOMS

 and

    telangiectasia
    SYMPTOMS

, and

    enzyme assay
    PARACLINICAL

 in patients with inexplicable complaints or findings.

    Carrier
    AGE

    females
    GENDER

 are most easily recognized by the presence of

    unique corneal opacities
    SYMPTOMS

.


Fabry's disease: report of a case.

Fabry's disease is a rare hereditary disorder of glycosphingolipid metabolism. Its clinical features have not been adequately described in Taiwan. This paper reports on a 32-year-old man who had painful acroparesthesia, disseminated skin angiokeratomas, whorled corneal opacity, mitral valve prolapse and renal insufficiency. There was also involvement of the central motor pathways and the autonomic nervous system. A sural nerve biopsy showed loss of small myelinated and unmyelinated fibers. A reduced serum activity of alpha-galactosidase A and a large amount of urinary globotriaosylceramide confirmed the diagnosis of Fabry's disease.

    Fabry's disease
    DIAGNOSIS

 is a

    rare hereditary
    GENETICS

    disorder of glycosphingolipid metabolism
    DIAGNOSIS

. Its clinical features have not been adequately described in

    Taiwan
    ETHNICITY

. This paper reports on a

    32-year-old
    AGE

    man
    GENDER

 who had

    painful acroparesthesia
    SYMPTOMS

,

    disseminated skin angiokeratomas
    SYMPTOMS

,

    whorled corneal opacity
    SYMPTOMS

,

    mitral valve prolapse
    SYMPTOMS

 and

    renal insufficiency
    SYMPTOMS

. There was also

    involvement of the central motor pathways and the autonomic nervous system
    SYMPTOMS

. A

    sural nerve biopsy
    PARACLINICAL

 showed

    loss of small myelinated and unmyelinated fibers
    MICROSCOPIC

. A

    reduced serum activity of alpha-galactosidase A
    BIOCHEMICAL

 and a

    large amount of urinary globotriaosylceramide
    BIOCHEMICAL

 confirmed the diagnosis of

    Fabry's disease
    DIAGNOSIS

.


[Fabry disease, an ophthalmo-neuro-dermato-cardio-nephrologic problem].

We want to present a 47-years-old patient suffering of a histologically and biochemically confirmed M. Fabry. Besides the ocular findings, we list the systemic findings and discuss the diagnostic and therapeutic possibilities. We especially want to point out the interdisciplinary collaboration in dealing with this condition.

We want to present a

    47-years-old
    AGE

 patient suffering of a histologically and biochemically confirmed

    M. Fabry
    DIAGNOSIS

. Besides the ocular findings, we list the systemic findings and discuss the diagnostic and therapeutic possibilities. We especially want to point out the interdisciplinary collaboration in dealing with this condition.


Successful treatment of painful crises of Fabry disease with low dose morphine.

Fabry disease is an X-linked disorder characterized in childhood by angiokeratoma, corneal opacities, and pain. At age 7 years our patient began experiencing an intermittent intense "burning" sensation within his feet and hands (acroparesthesias). Treatment with aspirin, acetaminophen, acetominophen with codeine, and phenytoin was unsuccessful. Carbamazepine and phenytoin reduced the frequency and duration of painful crises to 3-4 times annually. A treatment plan was developed consisting of a low-dose morphine infusion with increasing dosage until pain was relieved. Over the subsequent 28 months, we have had experienced treating 7 crises with morphine given as 0.06 mg/kg IV push, followed by a continuous infusion of 0.02 mg/kg/hr with amitriptyline 0.25 mg/kg at bedtime. Pain control is immediate, with the infusion gradually tapered after 24 hours.

    Fabry disease
    DIAGNOSIS

 is an

    X-linked disorder
    GENETICS

 characterized in

    childhood
    AGE

 by

    angiokeratoma
    SYMPTOMS

,

    corneal opacities
    SYMPTOMS

, and

    pain
    SYMPTOMS

. At

    age 7 years
    AGE

 our patient began experiencing an

    intermittent intense "burning" sensation within his feet and hands (acroparesthesias)
    SYMPTOMS

.

    Treatment with aspirin, acetaminophen, acetominophen with codeine
    NEG_FINDINGS

    , and phenytoin was unsuccessful
    NEG_FINDINGS

.

    Carbamazepine and phenytoin
    MEDICATION

    reduced the frequency and duration of painful crises to 3-4 times annually
    SYMPTOMS

. A treatment plan was developed consisting of a

    low-dose morphine infusion with increasing dosage
    MEDICATION

 until

    pain was relieved
    SYMPTOMS

. Over the subsequent 28 months, we have had experienced

    treating 7 crises
    SYMPTOMS

 with

    morphine given as 0.06 mg/kg IV push, followed by a continuous infusion of 0.02 mg/kg/hr with amitriptyline 0.25 mg/kg at bedtime
    MEDICATION

.

    Pain control
    SYMPTOMS

 is immediate, with the

    infusion gradually tapered after 24 hours
    MEDICATION

.


Sudden death in elderly women with Fabry's disease.

We report two cases of elderly women who died unexpectedly. In both cases, light- and electron-microscopical examination proved a diagnosis of Fabry's disease. The major pathological changes were myocardial mottling, foamy vacuolation of myocytes and glomerular endothelial cells, and characteristic lamellar inclusions. Neither woman had either a personal or family history of Fabry's disease. Fabry's disease presenting as sudden death is very rare. We present the findings in two cases together with a review of literature particularly relevant to the cardiovascular system.

We report two cases of

    elderly
    AGE

    women
    GENDER

 who

    died
    SYMPTOMS

    unexpectedly
    SYMPTOMS

. In both cases,

    light- and electron-microscopical examination
    PARACLINICAL

 proved a diagnosis of

    Fabry's disease
    DIAGNOSIS

. The major pathological changes were

    myocardial mottling
    SYMPTOMS

,

    foamy vacuolation of myocytes and glomerular endothelial cells
    MICROSCOPIC

, and

    characteristic lamellar inclusions
    MICROSCOPIC

. Neither

    woman
    GENDER

    had either a personal or family history of Fabry's disease
    FAMILY

.

    Fabry's disease
    DIAGNOSIS

 presenting as

    sudden death
    SYMPTOMS

 is very rare. We present the findings in two cases together with a review of literature particularly relevant to the cardiovascular system.

died
unexpectedly
myocardial mottling
sudden death


A histochemical and electron microscopic study of skeletal and cardiac muscle from a Fabry disease patient and carrier.

Histochemical and electron microscopic studies were performed in an attempt to clarify the muscle pathology in an 18-year-old man with Fabry disease, showing proximal limb muscle atrophy, and his 52-year-old mother, who is a Fabry carrier with hypertrophic cardiomyopathy. Despite the relatively mild myopathic changes revealed by histochemistry, electron microscopy demonstrated the widespread accumulation of abundant lamellated bodies in myofibers, associated with increased glycogen granules and autophagic vacuoles. The cardiac muscle of the proband's mother revealed a mosaic pattern of normal-appearing and hypertrophic myofibers containing a number of ring-like, lamellated bodies. Although further studies are necessary to support our findings, skeletal muscle is apparently involved in patients with Fabry disease, and a mosaic pattern of cardiac muscle involvement possibly reflecting Lyonization, may be one of the characteristic findings of a Fabry disease carrier.

    Histochemical and electron microscopic studies
    PARACLINICAL

 were performed in an attempt to clarify the muscle pathology in an

    18-year-old
    AGE

    man
    GENDER

 with

    Fabry disease
    DIAGNOSIS

, showing

    proximal limb muscle atrophy
    SYMPTOMS

, and

    his
    GENDER

    52-year-old
    AGE

    mother
    GENDER

,

    who is a Fabry carrier with hypertrophic cardiomyopathy
    FAMILY

.

    Despite the relatively mild myopathic changes
    NEG_FINDINGS

 revealed by

    histochemistry
    PARACLINICAL

,

    electron microscopy
    PARACLINICAL

 demonstrated the

    widespread accumulation of abundant lamellated bodies in myofibers, associated with increased glycogen granules and autophagic vacuoles
    MICROSCOPIC

. The

    cardiac muscle
    PARACLINICAL

 of the proband's mother revealed a

    mosaic pattern of normal-appearing and hypertrophic myofibers containing a number of ring-like, lamellated bodies
    MICROSCOPIC

. Although further studies are necessary to support our findings,

    skeletal muscle
    SYMPTOMS

 is apparently involved in patients with

    Fabry disease
    DIAGNOSIS

, and a

    mosaic pattern of cardiac muscle involvement
    SYMPTOMS

 possibly reflecting

    Lyonization
    SYMPTOMS

, may be one of the characteristic findings of a

    Fabry disease
    DIAGNOSIS

 carrier.

Fabry disease
Fabry disease
Fabry disease


Histopathologic and ultrastructural studies of angiokeratoma corporis diffusum in Kanzaki disease.

A novel metabolic disease, angiokeratoma corporis diffusum (Kanzaki), was the subject of an extensive histopathologic and ultrastructural study. Findings included dilated lymph and blood vessels in the upper dermis with an orthokeratortic, thickened, horny layer in well developed angiokeratoma. In the early papules, a few sporadic dyskeratotic keratinocytes were present in the epidermis with or without a thickened horny layer. Vesicular clear vacuolation was clearly observed in the cytoplasm of the secretory portion of the eccrine sweat glands, but none was observed in the vascular endothelial cells with hematoxylin-eosin staining. Using electron microscopy, lysosomal vacuolation was observed in many cell types, including eccrine sweat gland cells, vascular endothelial cells, dermal fibroblasts, dermal neural cells, lymphocytes of peripheral blood in the skin, and glomerular endothelial cells, but none was noted in the epithelial cells of the kidney. Widely dilated vacuoles were found to contain only a small amount of fuzzy filamentous material in the vascular endothelial cells, filamentous or electron-dense granular substances in fibroblasts, and electron-dense, lamellated or homogeneous structures in eccrine sweat gland cells and in neural cells. Ultracytochemical examination revealed glycoconjugates in dilated lysosomes. Characteristics of Kanzaki Disease were shown to differ from those of Fabry disease or any other lysosomal storage disease.

A

    novel metabolic disease
    DIAGNOSIS

,

    angiokeratoma corporis diffusum (Kanzaki)
    DIAGNOSIS

, was the subject of an extensive

    histopathologic and ultrastructural study
    PARACLINICAL

. Findings included

    dilated lymph and blood vessels in the upper dermis with an orthokeratortic, thickened, horny layer in well developed angiokeratoma
    MICROSCOPIC

. In the

    early papules
    SYMPTOMS

,

    a few sporadic dyskeratotic keratinocytes were present in the epidermis with or without a thickened horny layer
    MICROSCOPIC

.

    Vesicular clear vacuolation was clearly observed in the cytoplasm of the secretory portion of the eccrine sweat glands
    MICROSCOPIC

, but

    none was observed in the vascular endothelial cells
    NEG_FINDINGS

 with

    hematoxylin-eosin staining
    PARACLINICAL

. Using

    electron microscopy
    PARACLINICAL

,

    lysosomal vacuolation was observed in many cell types, including eccrine sweat gland cells, vascular endothelial cells, dermal fibroblasts, dermal neural cells, lymphocytes of peripheral blood in the skin, and glomerular endothelial cells
    MICROSCOPIC

, but

    none was noted in the epithelial cells of the kidney
    NEG_FINDINGS

.

    Widely dilated vacuoles were found to contain only a small amount of fuzzy filamentous material in the vascular endothelial cells, filamentous or electron-dense granular substances in fibroblasts, and electron-dense, lamellated or homogeneous structures in eccrine sweat gland cells and in neural cells
    MICROSCOPIC

.

    Ultracytochemical examination
    PARACLINICAL

 revealed

    glycoconjugates in dilated lysosomes
    MICROSCOPIC

. Characteristics of

    Kanzaki Disease
    DIAGNOSIS

 were shown to differ from those of

    Fabry disease
    DIAGNOSIS

 or any other

    lysosomal storage disease
    DIAGNOSIS

.


[Childhood acromelalgia a propos of a case revealing Fabry's disease].

The occurrence of an acrosyndrome (Raynaud's phenomenon, erythermalgia, acrodynia...) in childhood may be the first manifestation of a general disease. Though it can be an early onset Raynaud's disease, it could also be the first sign of a connective tissue disease (juvenile polyarthritis, mixed connectivitis...) or of a overload disorder. We report a case of childhood-onset acromelalgia leading to the discovery of Fabry's disease. This chromosome X-linked hereditary disorder, resulting in the ubiquitous accumulation of neutral sphingolipids, is usually rapidly suspected by the finding of "boxer-short" angiokeratoma. Diagnosis is confirmed by the ophthalmic examination (cornea verticillata), by the pathological examination of a skin sample, and by the measure of alpha-galactosidase A activity. Treatment is usually only symptomatic, but the discovery of the mutations responsible for the disease could open the way to specific therapy.

The

    occurrence of an acrosyndrome (Raynaud's phenomenon
    SYMPTOMS

,

    erythermalgia
    SYMPTOMS

,

    acrodynia
    SYMPTOMS

...) in

    childhood
    AGE

 may be the first manifestation of a general disease. Though it can be an early onset

    Raynaud's disease
    DIAGNOSIS

, it could also be the first sign of a

    connective tissue disease
    DIAGNOSIS

 (

    juvenile polyarthritis
    DIAGNOSIS

,

    mixed connectivitis
    DIAGNOSIS

...) or of a

    overload disorder
    DIAGNOSIS

. We report a case of

    childhood-onset acromelalgia
    AGE

 leading to the discovery of

    Fabry's disease
    DIAGNOSIS

. This

    chromosome X-linked hereditary disorder
    GENETICS

, resulting in the

    ubiquitous accumulation of neutral sphingolipids
    MICROSCOPIC

, is usually rapidly suspected by the finding of

    "boxer-short" angiokeratoma
    SYMPTOMS

. Diagnosis is confirmed by the

    ophthalmic examination
    PARACLINICAL

 (

    cornea verticillata
    SYMPTOMS

), by the

    pathological examination of a skin sample
    PARACLINICAL

, and by the

    measure of alpha-galactosidase A activity
    PARACLINICAL

. Treatment is usually only symptomatic, but the discovery of the mutations responsible for the disease could open the way to specific therapy.

Raynaud's disease
connective tissue disease
juvenile polyarthritis
mixed connectivitis
overload disorder
Fabry's disease


Fabry-like laminated myelin body associated with IgA nephropathy.

We present the first female patient to exhibit Fabry-like myelin bodies in the glomerular epithelial cell in association with IgA nephropathy. This previously healthy 36-year-old woman presented with proteinuria and hematuria without skin lesions. Renal biopsy showed typical IgA nephropathy, with paramesangial deposits, mesangial proliferation and scattered myelin bodies. The leukocytic alpha-galactosidase A activity was abnormally low. She had no family history of Fabry's disease nor the characteristic features, such as skin lesion, neuralgia, or hypohidrosis. Fabry's disease is diagnosed from the renal biopsy findings and the activity of alpha-galactosidase A in leukocytes and/or fibroblasts. We diagnosed the present case with Fabry' disease and IgA nephropathy from these results.

We present the first

    female
    GENDER

 patient to exhibit

    Fabry-like myelin bodies in the glomerular epithelial cell
    MICROSCOPIC

 in association with

    IgA nephropathy
    DIAGNOSIS

. This previously healthy

    36-year-old
    AGE

    woman
    GENDER

 presented with

    proteinuria
    BIOCHEMICAL

 and

    hematuria
    BIOCHEMICAL

    without skin lesions
    NEG_FINDINGS

.

    Renal biopsy
    PARACLINICAL

 showed

    typical IgA nephropathy
    MICROSCOPIC

, with

    paramesangial deposits
    MICROSCOPIC

,

    mesangial proliferation
    MICROSCOPIC

 and

    scattered myelin bodies
    MICROSCOPIC

. The

    leukocytic alpha-galactosidase A activity was abnormally low
    BIOCHEMICAL

.

    She
    GENDER

 had

    no family history of Fabry's disease
    NEG_FINDINGS

 nor the characteristic features, such as

    skin lesion
    SYMPTOMS

,

    neuralgia
    SYMPTOMS

, or

    hypohidrosis
    SYMPTOMS

.

    Fabry's disease
    DIAGNOSIS

 is diagnosed from the

    renal biopsy
    PARACLINICAL

 findings and the

    activity of alpha-galactosidase A in leukocytes and/or fibroblasts
    BIOCHEMICAL

. We diagnosed the present case with

    Fabry' disease and IgA nephropathy
    DIAGNOSIS

 from these results.

IgA nephropathy
Fabry's disease
Fabry' disease and IgA nephropathy

without skin lesions
no family history of Fabry's disease


Fabry's disease: clinical, pathologic and biochemical manifestations in two Chinese males.

Fabry's disease is a rare hereditary disease transmitted as an X-linked recessive trait with the primary metabolic defect of an enzyme alpha-galactosidase A, resulting in deposition of glycolipids (ceramide trihexoside) in various tissues, including the kidneys. Two sibling cases of Chinese adult male patients in a family with Fabry's disease were completely evaluated including the clinical, pathologic and biochemical studies. Both of the patients had the similar clinical manifestations such as telangiectases, proteinuria, acral pains, corneal opacities, tortuous renal vessels and recurrent fever. Chronic renal insufficiency was noted in Case 1, whereas Case 2 had normal renal function. Microscopic hematuria was noted in Case 1. In renal biopsy, LM showed foamy vacuolation of the glomerular visceral epithelial cells and EM showed widespread myelin bodies (Zebra bodies) in kidney tissues, most numerous in visceral epithelia in both cases. Those findings are diagnostic for Fabry's disease. The plasma activity of alpha-galactosidase of Case 1 was 0.8 and that of Case 2 was 1.0 (normal reference range: 8.5-18.5 nmol/hr/min). The plasma activity of alpha-galactosidase A of Case 1 was 0.4 and that of Case 2 was 0.8 (normal reference range: 7.9-16.9 nmol/hr/min). All the enzyme activities in both cases were much lower than those of normal subjects. In addition to clinical presentations, pathologic study and biochemical study with assays of plasma or serum activities of alpha-galactosidase and alpha-galactosidase A are important steps in the diagnosis of Fabry's disease.(ABSTRACT TRUNCATED AT 250 WORDS)

    Fabry's disease
    DIAGNOSIS

 is a

    rare hereditary disease transmitted as an X-linked recessive trait
    GENETICS

 with the primary

    metabolic defect of an enzyme alpha-galactosidase A
    GENETICS

, resulting in

    deposition of glycolipids (ceramide trihexoside) in various tissues, including the kidneys
    MICROSCOPIC

. Two sibling cases of

    Chinese
    ETHNICITY

    adult
    AGE

    male
    GENDER

 patients

    in a family with Fabry's disease
    FAMILY

 were completely evaluated including the clinical, pathologic and biochemical studies. Both of the patients had the similar clinical manifestations such as

    telangiectases
    SYMPTOMS

,

    proteinuria
    BIOCHEMICAL

,

    acral pains
    SYMPTOMS

,

    corneal opacities
    SYMPTOMS

,

    tortuous renal vessels
    SYMPTOMS

 and

    recurrent fever
    SYMPTOMS

.

    Chronic renal insufficiency
    SYMPTOMS

 was noted in Case 1, whereas Case 2 had

    normal renal function
    NEG_FINDINGS

.

    Microscopic hematuria
    BIOCHEMICAL

 was noted in Case 1. In

    renal biopsy
    PARACLINICAL

,

    LM
    PARACLINICAL

 showed

    foamy vacuolation of the glomerular visceral epithelial cells
    MICROSCOPIC

 and

    EM
    PARACLINICAL

 showed

    widespread myelin bodies (Zebra bodies) in kidney tissues, most numerous in visceral epithelia
    MICROSCOPIC

 in both cases. Those findings are diagnostic for

    Fabry's disease
    DIAGNOSIS

. The

    plasma activity of alpha-galactosidase of
    BIOCHEMICAL

 Case 1

    was 0.8 and that of
    BIOCHEMICAL

 Case 2

    was 1.0 (normal reference range: 8.5-18.5 nmol/hr/min)
    BIOCHEMICAL

.

    The plasma activity of alpha-galactosidase A of
    BIOCHEMICAL

 Case 1

    was 0.4 and that of
    BIOCHEMICAL

 Case 2

    was 0.8 (normal reference range: 7.9-16.9 nmol/hr/min)
    BIOCHEMICAL

.

    All the enzyme activities
    BIOCHEMICAL

 in both cases

    were much lower than those of normal subjects
    BIOCHEMICAL

. In addition to clinical presentations,

    pathologic study
    PARACLINICAL

 and

    biochemical study
    PARACLINICAL

 with

    assays of plasma or serum activities of alpha-galactosidase and alpha-galactosidase A
    BIOCHEMICAL

 are important steps in the diagnosis of Fabry's disease.(ABSTRACT TRUNCATED AT 250 WORDS)

telangiectases
acral pains
corneal opacities
tortuous renal vessels
recurrent fever
Chronic renal insufficiency


Central retinal artery occlusion in a patient with Fabry's disease documented by scanning laser ophthalmoscopy.

Fabry's disease, angiokeratoma corporis diffusum, is an X-linked inborn error of glycosphingolipid metabolism due to lack of activity of the lysosomal enzyme, alpha-galactosidase A, resulting in progressive intracellular deposition of neutral glycosphingolipids in various tissues, including vascular endothelial - and smooth muscle cells. Occlusions of the retinal vessels are rare. We present a case of central retinal artery occlusion in a 25-year-old male with Fabry's disease, documented by fluorescein- and indocyanine green angiography performed by scanning laser opththalmoscopy.

    Fabry's disease
    DIAGNOSIS

,

    angiokeratoma corporis diffusum
    SYMPTOMS

, is an

    X-linked inborn error of glycosphingolipid metabolism
    GENETICS

 due to

    lack of activity of the lysosomal enzyme, alpha-galactosidase A
    BIOCHEMICAL

, resulting in

    progressive intracellular deposition of neutral glycosphingolipids in various tissues, including vascular endothelial - and smooth muscle cells
    MICROSCOPIC

.

    Occlusions of the retinal vessels
    SYMPTOMS

 are rare. We present a case of

    central retinal artery occlusion
    SYMPTOMS

 in a

    25-year-old
    AGE

    male
    GENDER

 with

    Fabry's disease
    DIAGNOSIS

, documented by

    fluorescein- and indocyanine green angiography
    PARACLINICAL

 performed by

    scanning laser opththalmoscopy
    PARACLINICAL

.

angiokeratoma corporis diffusum
Occlusions of the retinal vessels
central retinal artery occlusion


[An autopsied case of Fabry's disease presenting with parkinsonism and cardiomegaly as a cardinal clinical manifestation].

A 68-year-old male had been followed up under a clinical diagnosis of parkinsonism for 5 years. He was admitted to the Kanto Teishin Hospital with a chief complaint of difficulty in swallowing. Physical findings were almost normal. Neurological examination showed parkinsonism including mask-like face, positive Myerson's sign, mild rigidity, marche à petit pas, and retropulsion, and pyramidal signs including mild right hemiparesis, generalized hyperreflexia and positive Babinski's sign on both sides. Routine blood analysis was normal, except for elevated LDH level. He was found to have cardiac enlargement (CTR 58.7%) in chest roentogenogram, left ventricular hypertrophy (LVH), right bundle branch block and myocardial ischemia in electrocardiogram, as well as LVH, asymmetrical septal hypertrophy, mild MR and AR in echocardiogram. A T2 weighted brain MRI disclosed multiple high signal intensities in the basal ganglia and deep white matter regions which suggest parkinsonism resulting from multiple cerebral infarctions. An upper gastrointestinal endoscopic examination revealed esophageal and gastric carcinomas. He died of ventricular fibrillation 14 days after an operation of these carcinomas. Autopsy showed severe cardiomegaly (800 g) and vacuolar change of myocardium with lamellar body on electron microscopic examination. A definite biochemical diagnosis of Fabry's disease was made by demonstration of deposition of a large amount of trihexosylceramide in the myocardium, kidney, and liver. This case presented parkinsonism and cardiomegaly without typical signs of Fabry's disease. Therefore, Fabry's disease should be considered as one of possible underlying diseases, when a patient has cardiomegaly or ischemic cerebrovascular disease without risk factors, even if he has no typical signs of Fabry's disease.

A

    68-year-old
    AGE

    male
    GENDER

 had been followed up under a clinical diagnosis of

    parkinsonism
    DIAGNOSIS

 for 5 years.

    He
    GENDER

 was admitted to the Kanto Teishin Hospital with a chief complaint of

    difficulty in swallowing
    SYMPTOMS

.

    Physical findings were almost normal
    NEG_FINDINGS

.

    Neurological examination
    PARACLINICAL

 showed

    parkinsonism
    SYMPTOMS

 including

    mask-like face
    SYMPTOMS

,

    positive Myerson's sign
    SYMPTOMS

,

    mild rigidity
    SYMPTOMS

,

    marche à petit pas
    SYMPTOMS

, and

    retropulsion
    SYMPTOMS

, and

    pyramidal signs
    SYMPTOMS

 including

    mild right hemiparesis
    SYMPTOMS

,

    generalized hyperreflexia
    SYMPTOMS

 and

    positive Babinski's sign on both sides
    SYMPTOMS

.

    Routine blood analysis was normal
    NEG_FINDINGS

, except for

    elevated LDH level
    BIOCHEMICAL

.

    He
    GENDER

 was found to have

    cardiac enlargement (CTR 58.7%) in chest roentogenogram
    SYMPTOMS

,

    left ventricular hypertrophy (LVH)
    SYMPTOMS

,

    right bundle branch block
    SYMPTOMS

 and

    myocardial ischemia
    SYMPTOMS

 in

    electrocardiogram
    SYMPTOMS

, as well as

    LVH
    SYMPTOMS

,

    asymmetrical septal hypertrophy
    SYMPTOMS

,

    mild MR and AR
    SYMPTOMS

 in

    echocardiogram
    SYMPTOMS

. A

    T2 weighted brain MRI
    PARACLINICAL

 disclosed

    multiple high signal intensities in the basal ganglia and deep white matter regions
    SYMPTOMS

 which suggest

    parkinsonism
    DIAGNOSIS

 resulting from

    multiple cerebral infarctions
    SYMPTOMS

. An

    upper gastrointestinal endoscopic examination
    PARACLINICAL

 revealed

    esophageal and gastric carcinomas
    DIAGNOSIS

.

    He
    GENDER

    died
    SYMPTOMS

 of

    ventricular fibrillation
    SYMPTOMS

 14 days after an

    operation of these carcinomas
    MEDICATION

.

    Autopsy
    PARACLINICAL

 showed

    severe cardiomegaly (800 g)
    SYMPTOMS

 and

    vacuolar change of myocardium with lamellar body
    MICROSCOPIC

 on

    electron microscopic examination
    PARACLINICAL

. A definite biochemical diagnosis of

    Fabry's disease
    DIAGNOSIS

 was made by demonstration of

    deposition of a large amount of trihexosylceramide in the myocardium, kidney, and liver
    MICROSCOPIC

. This case presented

    parkinsonism
    DIAGNOSIS

 and

    cardiomegaly
    SYMPTOMS

    without typical signs of Fabry's disease
    NEG_FINDINGS

. Therefore,

    Fabry's disease
    DIAGNOSIS

 should be considered as one of possible underlying diseases, when a patient has

    cardiomegaly
    SYMPTOMS

 or

    ischemic cerebrovascular disease
    SYMPTOMS

    without risk factors
    NEG_FINDINGS

, even if he has

    no typical signs of Fabry's disease
    NEG_FINDINGS

.

parkinsonism
parkinsonism
esophageal and gastric carcinomas
Fabry's disease
parkinsonism
Fabry's disease


Fabry's disease in a female carrier with bilateral thalamic infarcts: a case report and a family study.

An unusual case of a young woman, heterozygote for Fabry gene is reported, who presented bilateral thalamic infarcts due to occlusions of central nervous system vessels. Three other members of her family were studied. Fabry's disease (angiokeratoma corporis diffusum) is included among the rare causes of ischemic stroke in young adults.

An unusual case of a

    young
    AGE

    woman
    GENDER

,

    heterozygote for Fabry gene
    GENETICS

 is reported, who presented

    bilateral thalamic infarcts due to occlusions of central nervous system vessels
    SYMPTOMS

. Three other members of

    her
    GENDER

 family were studied.

    Fabry's disease
    DIAGNOSIS

 (

    angiokeratoma corporis diffusum)
    DIAGNOSIS

 is included among the rare causes of

    ischemic stroke
    SYMPTOMS

 in

    young adults
    AGE

.

Fabry's disease
angiokeratoma corporis diffusum)


[Fabry disease: systemic deposition of a glycolipid].

A 20-year-old man was admitted with telangiectatic skin lesions over the lower abdomen, buttocks and genitals and also hypohidrosis and heat intolerance. Fabry disease was diagnosed on the basis of biochemical and histopathological analyses. The concentration of urinary trihexosyl-ceramide was increased but the activity of galactosidase in serum, urine and lymphocytes was marginal. Typical lipid inclusions, showing a concentrically arranged, lamellar osmiophilic structure were identified by electron microscopy in the cytoplasm of endothelial cells from affected skin.

A

    20-year-old
    AGE

    man
    GENDER

 was admitted with

    telangiectatic skin lesions over the lower abdomen, buttocks and genitals
    SYMPTOMS

 and also

    hypohidrosis
    SYMPTOMS

 and

    heat intolerance
    SYMPTOMS

.

    Fabry disease
    DIAGNOSIS

 was diagnosed on the basis of

    biochemical and histopathological analyses
    PARACLINICAL

. The

    concentration of urinary trihexosyl-ceramide was increased
    BIOCHEMICAL

 but the

    activity of galactosidase in serum, urine and lymphocytes was marginal
    BIOCHEMICAL

.

    Typical lipid inclusions, showing a concentrically arranged, lamellar osmiophilic structure were identified
    MICROSCOPIC

 by

    electron microscopy
    PARACLINICAL

    in the cytoplasm of endothelial cells from affected skin
    MICROSCOPIC

.


A case of Fabry disease (alpha-galactosidase A deficiency).

Fabry disease is a rare lipid storage disorder, often silent until adulthood. We report the case of a rural, primary care patient whose initial presentation was that of progressive weakness from anemia. The anemia was determined to be of renal origin, and led to a diagnosis of Fabry disease. Although less than 500 cases of this disease have been reported in the literature, such events remind the clinician that the environment of rural practice is not immune to unusual and diverse medical problems.

    Fabry disease
    DIAGNOSIS

 is a

    rare lipid storage disorder
    DIAGNOSIS

, often silent until

    adulthood
    AGE

. We report the case of a

    rural
    ETHNICITY

, primary care patient whose initial presentation was that of

    progressive weakness
    SYMPTOMS

 from

    anemia
    BIOCHEMICAL

. The

    anemia
    BIOCHEMICAL

 was determined to be of

    renal origin
    BIOCHEMICAL

, and led to a diagnosis of

    Fabry disease
    DIAGNOSIS

. Although less than 500 cases of this disease have been reported in the literature, such events remind the clinician that the environment of rural practice is not immune to unusual and diverse medical problems.

Fabry disease
rare lipid storage disorder
Fabry disease


Possible thyroidal involvement in a case of Fabry disease.

Endocrinological evaluations of a 48-year-old man with Fabry disease revealed low levels of serum thyroid hormones and high levels of serum thyrotropin (TSH), indicating that the patient had primary hypothyroidism. Also, an exaggerated growth hormone (GH) response to hypoglycemic stimuli was observed. Thin layer chromatography of the lipid extract of the thyroid gland obtained by biopsy demonstrated marked accumulation of ceramide trihexoside (CTH) and ceramide dihexoside (CDH). These findings strongly suggest that thyroid hypofunction and hypothalamic dysfunction could be involved in Fabry disease.

    Endocrinological evaluations
    PARACLINICAL

 of a

    48-year-old
    AGE

    man
    GENDER

 with

    Fabry disease
    DIAGNOSIS

 revealed

    low levels of serum thyroid hormones
    BIOCHEMICAL

 and

    high levels of serum thyrotropin (TSH)
    BIOCHEMICAL

, indicating that the patient had

    primary hypothyroidism
    DIAGNOSIS

. Also, an

    exaggerated growth hormone (GH) response to hypoglycemic stimuli
    BIOCHEMICAL

 was observed.

    Thin layer chromatography of the lipid extract of the thyroid gland obtained by biopsy
    PARACLINICAL

 demonstrated

    marked accumulation of ceramide trihexoside (CTH) and ceramide dihexoside (CDH)
    MICROSCOPIC

. These findings strongly suggest that

    thyroid hypofunction
    SYMPTOMS

 and

    hypothalamic dysfunction
    SYMPTOMS

 could be involved in

    Fabry disease
    DIAGNOSIS

.

Fabry disease
primary hypothyroidism
Fabry disease

thyroid hypofunction
hypothalamic dysfunction


Small bowel ischaemia in Fabry's disease.

A patient with previously diagnosed Fabry's disease and a long history of post-prandial abdominal pain died following small bowel infarction. Post-mortem demonstrated Fabry's type deposits in the small vessels and nerves supplying the bowel but in addition, a localized atheromatous stenosis of the superior mesenteric artery. In retrospect, his terminal illness and possibly his chronic symptoms were related to the latter finding. Angioplasty to the superior mesenteric artery may have been of benefit. Mesenteric angiography should be considered in patients with chronic post-prandial pain because large vessel disease may coexist with other a priori pathologies and is imminently treatable.

A patient with previously diagnosed

    Fabry's disease
    DIAGNOSIS

 and a

    long history of post-prandial abdominal pain
    SYMPTOMS

    died
    SYMPTOMS

 following

    small bowel infarction
    SYMPTOMS

.

    Post-mortem
    PARACLINICAL

 demonstrated

    Fabry's type deposits in the small vessels and nerves supplying the bowel
    MICROSCOPIC

 but in addition, a

    localized atheromatous stenosis of the superior mesenteric artery
    SYMPTOMS

. In retrospect,

    his
    GENDER

    terminal illness
    SYMPTOMS

 and possibly his

    chronic symptoms
    SYMPTOMS

 were related to the latter finding.

    Angioplasty to the superior mesenteric artery
    MEDICATION

 may have been of benefit.

    Mesenteric angiography
    PARACLINICAL

 should be considered in patients with

    chronic post-prandial pain
    SYMPTOMS

 because

    large vessel disease
    SYMPTOMS

 may coexist with other a priori pathologies and is imminently treatable.


Capillary changes in angiokeratoma corporis diffusum Fabry.

We report on capillary changes on the Sulcus matricis unguis in a patient with an established angiokeratoma corporis diffusum Fabry. A fasciculated ramification of the capillary in 2-5 loops, which is not found in healthy individuals and that until now has solely been described in patients with vasculitis, was detected. The question now arises whether these are initial changes in the disease which later lead to manifested angiokeratomas. Further investigations will show if, and to what extent, these observations can contribute to further clarification of the developmental method of acroparaethesiae, which are part of the principal signs of Morbus Fabry.

We report on

    capillary changes on the Sulcus matricis unguis
    SYMPTOMS

 in a patient with an established

    angiokeratoma corporis diffusum Fabry
    SYMPTOMS

. A

    fasciculated ramification of the capillary in 2-5 loops
    SYMPTOMS

, which is not found in healthy individuals and that until now has solely been described in patients with

    vasculitis
    DIAGNOSIS

, was detected. The question now arises whether these are initial changes in the disease which later lead to manifested

    angiokeratomas
    SYMPTOMS

. Further investigations will show if, and to what extent, these observations can contribute to further clarification of the developmental method of

    acroparaethesiae
    SYMPTOMS

, which are part of the principal signs of

    Morbus Fabry
    DIAGNOSIS

.


An arthroplastic salvage procedure for combined radiocarpal and distal radioulnar pathology.

In a patient with silicone synovitis and degeneration of the distal radioulnar joint after 2 operative procedures for Kienböck's disease, and in a patient with long-standing scapholunate dissociation and distal radioulnar degenerative arthritis, a combined salvage arthroplasty was performed. A proximal row carpectomy with a Sauvé Kapandji procedure maintained reasonable function.

In a patient with

    silicone synovitis
    SYMPTOMS

 and

    degeneration of the distal radioulnar joint
    SYMPTOMS

 after

    2 operative procedures for Kienböck's disease
    MEDICATION

, and in a patient with

    long-standing scapholunate dissociation
    SYMPTOMS

 and

    distal radioulnar degenerative arthritis
    DIAGNOSIS

, a

    combined salvage arthroplasty
    MEDICATION

 was performed.

    A proximal row carpectomy with a Sauvé Kapandji procedure
    MEDICATION

    maintained reasonable function
    SYMPTOMS

.


Stroke in Fabry's disease.

This study was performed to characterize the frequency, clinical presentation and etiology of cerebrovascular complications in patients with Fabry's disease. Thirty-three patients (age range 6-64 years) with Fabry's disease were reviewed, eight (24%) of whom suffered cerebrovascular complications. All patients developed ischemic strokes involving small arterial vessels which occurred in equal frequency in carotid and vertebrobasilar distributions. In six of these eight patients, a stroke occurred prior to age 40 years. Stroke frequently complicates Fabry's disease and represents a significant source of morbidity in patients affected with this condition; it usually involves thrombosis of small arteries affected by the disease process.

This study was performed to characterize the frequency, clinical presentation and etiology of

    cerebrovascular complications
    SYMPTOMS

 in patients with

    Fabry's disease
    DIAGNOSIS

. Thirty-three patients (

    age range 6-64 years
    AGE

) with

    Fabry's disease
    DIAGNOSIS

 were reviewed, eight (24%) of whom suffered

    cerebrovascular complications
    SYMPTOMS

. All patients developed

    ischemic strokes involving small arterial vessels
    SYMPTOMS

 which occurred in equal frequency

    in carotid and vertebrobasilar distributions
    SYMPTOMS

. In six of these eight patients, a

    stroke
    SYMPTOMS

 occurred

    prior to age 40 years
    AGE

.

    Stroke
    SYMPTOMS

 frequently complicates

    Fabry's disease
    DIAGNOSIS

 and represents a significant source of morbidity in patients affected with this condition; it usually involves

    thrombosis of small arteries affected by the
    SYMPTOMS

 disease process.

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


Monostotic localization of Paget disease in the hand.

Paget disease rarely affects the hand and when it does, there is usually a polyosteotic involvement. Only a few cases have been described in the literature on monostotic localization in the hand. This paper adds two cases with solitary involvement of a metacarpal.

    Paget disease
    DIAGNOSIS

 rarely affects the hand and when it does, there is usually a

    polyosteotic involvement
    SYMPTOMS

. Only a few cases have been described in the literature on

    monostotic localization in the hand
    SYMPTOMS

. This paper adds two cases with

    solitary involvement of a metacarpal
    SYMPTOMS

.

polyosteotic involvement
monostotic localization in the hand
solitary involvement of a metacarpal


Complex arylsulfatase A alleles causing metachromatic leukodystrophy.

Metachromatic leukodystrophy is a lysosomal storage disorder caused by the deficiency of arylsulfatase A. Sequencing of the arylsulfatase A genes of a patient affected with late infantile metachromatic leukodystrophy revealed that the patient is a compound heterozygote of two alleles carrying two deleterious mutation each. One allele bears a splice donor site mutation together with two polymorphisms and an additional missense mutation (Gly122 > Ser). The splice donor site mutation and the Gly122 > Ser substitution have been described recently but on different alleles. The other allele carries two missense mutations causing a Gly154 > Asp and a Pro167 > Arg substitution. When arylsulfatase A cDNAs carrying these mutations separately or in combination were transfected into baby hamster kidney cells expression of arylsulfatase A activity could not be detected. Linkage of mutations was verified by sequencing of the parental DNAs. Biosynthesis studies performed with the patients' fibroblasts show that the enzyme carrying both mutations is synthesized in almost normal amounts but is rapidly degraded in an early biosynthetic compartment. The occurence of two disease causing mutations on the same allele is a novel phenomenon in metachromatic leukodystrophy and as far as lysosomal storage diseases are concerned have so far only been described in Fabry disease and in the complex glucocerebrosidase alleles associated with Gaucher disease.

    Metachromatic leukodystrophy
    SYMPTOMS

 is a

    lysosomal storage disorder
    DIAGNOSIS

 caused by the deficiency of arylsulfatase A.

    Sequencing of the arylsulfatase A genes
    PARACLINICAL

 of a patient affected with

    late infantile metachromatic leukodystrophy
    DIAGNOSIS

 revealed that the patient is a

    compound heterozygote of two alleles carrying two deleterious mutation each
    GENETICS

.

    One allele bears a splice donor site mutation together with two polymorphisms and an additional missense mutation (Gly122 > Ser)
    GENETICS

. The

    splice donor site mutation and the Gly122 > Ser substitution
    GENETICS

 have been described recently but on different alleles. The

    other allele carries two missense mutations causing a Gly154 > Asp and a Pro167 > Arg substitution
    GENETICS

. When arylsulfatase A cDNAs carrying these mutations separately or in combination were transfected into

    baby hamster kidney cells
    MICROSCOPIC

    expression of arylsulfatase A activity could not be detected
    NEG_FINDINGS

.

    Linkage of mutations
    GENETICS

 was verified by

    sequencing of the parental DNAs
    PARACLINICAL

.

    Biosynthesis studies
    PARACLINICAL

 performed with the patients' fibroblasts show that the enzyme carrying both mutations is

    synthesized in almost normal amounts
    BIOCHEMICAL

    but is rapidly degraded in an early biosynthetic compartment
    MICROSCOPIC

. The

    occurence of two disease causing mutations on the same allele
    GENETICS

 is a novel phenomenon in

    metachromatic leukodystrophy
    SYMPTOMS

 and as far as

    lysosomal storage diseases
    DIAGNOSIS

 are concerned have so far only been described in

    Fabry disease
    DIAGNOSIS

 and in the

    complex glucocerebrosidase alleles
    GENETICS

 associated with

    Gaucher disease
    DIAGNOSIS

.

Metachromatic leukodystrophy
metachromatic leukodystrophy


Salmonella typhi osteomyelitis.

Salmonella infections in man can be divided in five clinical groups: enteric fever, septicaemia without localization, focal disease, gastroenteritis and the carrier state. Salmonella typhi is mostly associated with enteric fever and the carrier state. Bone infections due to S. typhi have been reported relatively seldom. They usually occur as the result of metastatic spread during septicaemia or, more rarely, after direct inoculation. Two patients with S. typhi osteomyelitis of the forearm without evidence of a primary infection or direct inoculation are presented here.

    Salmonella infections
    DIAGNOSIS

 in

    man
    GENDER

 can be divided in five clinical groups:

    enteric fever
    DIAGNOSIS

,

    septicaemia
    DIAGNOSIS

    without localization
    NEG_FINDINGS

,

    focal disease
    DIAGNOSIS

,

    gastroenteritis
    DIAGNOSIS

 and the carrier state.

    Salmonella typhi
    DIAGNOSIS

 is mostly associated with

    enteric fever
    DIAGNOSIS

 and the carrier state.

    Bone infections
    SYMPTOMS

    due to S. typhi
    DIAGNOSIS

 have been reported relatively seldom. They usually occur as the result of

    metastatic spread
    SYMPTOMS

 during

    septicaemia
    DIAGNOSIS

 or, more rarely, after

    direct inoculation
    SYMPTOMS

. Two patients with

    S. typhi osteomyelitis of the forearm
    DIAGNOSIS

    without evidence of a primary infection or direct inoculation
    NEG_FINDINGS

 are presented here.

Salmonella infections
enteric fever
septicaemia
focal disease
gastroenteritis
Salmonella typhi
enteric fever
due to S. typhi
septicaemia
S. typhi osteomyelitis of the forearm

Bone infections
metastatic spread
direct inoculation


Mild phenotypic expression of alpha-N-acetylgalactosaminidase deficiency in two adult siblings.

Two adult siblings with an alpha-N-acetylgalactosaminidase deficiency are described. The patients' major features are massive lymphoedema and angiokeratoma corporis diffusum. Neurological evaluation performed in one of the patients was considered within normal limits. Blood type is A positive in each case. Ultrastructural examination of skin revealed numerous vacuoles in endothelial cells and pericytes. Fibroblast activity of alpha-N-acetylgalactosaminidase was decreased to 0.6-2% of mean normal value. Chromatography of urinary oligosaccharides showed abnormal bands identical to those excreted by two infantile patients with Schindler disease. The bands were identified as sialyloligosaccharides, and gas chromatography revealed the presence of N-acetylgalactosamine-rich compounds accounting for 30% of the total monosaccharide content of the oligosaccharide fraction. These findings confirm the heterogeneity of alpha-N-acetylgalactosaminidase deficiency and emphasize the need to consider this lysosomal storage disease in the differential diagnosis of patients with angiokeratoma.

Two

    adult
    AGE

 siblings with an

    alpha-N-acetylgalactosaminidase deficiency
    BIOCHEMICAL

 are described. The patients' major features are

    massive lymphoedema
    SYMPTOMS

 and

    angiokeratoma corporis diffusum
    SYMPTOMS

.

    Neurological evaluation
    PARACLINICAL

 performed in one of the patients

    was considered within normal limits
    NEG_FINDINGS

.

    Blood type is A positive
    BIOCHEMICAL

 in each case.

    Ultrastructural examination of skin
    PARACLINICAL

 revealed

    numerous vacuoles in endothelial cells and pericytes
    MICROSCOPIC

.

    Fibroblast activity of alpha-N-acetylgalactosaminidase was decreased to 0.6-2% of mean normal value
    BIOCHEMICAL

.

    Chromatography of urinary oligosaccharides
    PARACLINICAL

 showed

    abnormal bands identical to those excreted by
    MICROSCOPIC

 two

    infantile
    AGE

 patients with

    Schindler disease
    DIAGNOSIS

. The bands were identified as

    sialyloligosaccharides
    MICROSCOPIC

, and

    gas chromatography
    PARACLINICAL

 revealed the

    presence of N-acetylgalactosamine-rich compounds accounting for 30% of the total monosaccharide content of the oligosaccharide fraction
    MICROSCOPIC

. These findings confirm the heterogeneity of

    alpha-N-acetylgalactosaminidase deficiency
    BIOCHEMICAL

 and emphasize the need to consider this

    lysosomal storage disease
    DIAGNOSIS

 in the

    differential diagnosis
    PARACLINICAL

 of patients with

    angiokeratoma
    SYMPTOMS

.

massive lymphoedema
angiokeratoma corporis diffusum
angiokeratoma

Schindler disease
lysosomal storage disease


Compound heterozygosity for hemoglobin C and Korle-Bu: moderate microcytic hemolytic anemia and acceleration of crystal formation [corrected].

We report here that compound heterozygosity for hemoglobin Korle-Bu (HbKB) and HbC (beta 6 Glu-->Lys) is associated with moderate chronic hemolytic anemia with microcytosis. To understand the pathogenesis of this syndrome, we have studied the effect of Hb Korle-Bu (KB = beta 73 Asp-->Asn) on the crystallization of HbC. We have previously established that fetal Hb (HbF) inhibits the crystallization of HbC. In contrast, HbS accelerates crystallization affecting the pathogenesis of SC disease. We now report on in vitro crystallization of mixtures of HbKB, HbC, and various amounts of HbF and the native hemolysate of a child who is a compound heterozygote for HbKB and HbC. At 6 months of age, the propositus' hemolysate contained 55% HbKB, 39% HbC, and 6% HbF. Crystal formed within 2 minutes compared with 30 minutes for the mixture of 40% HbC:60% HbS and with 180 minutes for 40% HbC:60% HbA. The morphology of the crystals formed was cubic, in contrast with the tetragonal crystals observed in CC and SC disease. Early crystals did not exhibit "sharp edges" until 45 minutes. Purified HbKB formed aggregates but not crystals after 24 hours. Isopycnic gradients showed that the KB/C compound heterozygotes have red blood cell (RBC) densities intermediate between the AC and CC phenotype and similar to SC disease. The surface residue beta 73, known to participate in areas of interaction of the deoxy HbS polymer, can now be assigned to areas of contact in HbC containing crystals. The hemolysis observed in the HbKB/C compound heterozygote is likely to be secondary to the acceleration of Hb crystallization. The microcytosis and increased RBC density is clearly the consequence of the presence of HbC, but the basis of the increased RBC pathology compared with AC trait, despite the low proportion of HbC (35% to 40%), remains to be elucidated.

We report here that

    compound heterozygosity for hemoglobin Korle-Bu (HbKB) and HbC (beta 6 Glu-->Lys)
    GENETICS

 is associated with

    moderate chronic hemolytic anemia
    BIOCHEMICAL

 with

    microcytosis
    BIOCHEMICAL

. To understand the pathogenesis of this syndrome, we have studied the effect of

    Hb Korle-Bu (KB = beta 73 Asp-->Asn)
    GENETICS

 on the crystallization of HbC. We have previously established that fetal Hb (HbF) inhibits the crystallization of HbC. In contrast,

    HbS accelerates crystallization
    BIOCHEMICAL

 affecting the pathogenesis of

    SC disease
    DIAGNOSIS

. We now report on

    in vitro crystallization of mixtures of HbKB, HbC, and various amounts of HbF
    PARACLINICAL

 and the native

    hemolysate
    BIOCHEMICAL

 of a

    child
    AGE

 who is a compound heterozygote for HbKB and HbC. At

    6 months of age
    AGE

, the propositus' hemolysate contained 55% HbKB, 39% HbC, and 6% HbF. Crystal formed within 2 minutes compared with 30 minutes for the mixture of

    40% HbC:60% HbS
    MEDICATION

 and with 180 minutes for 40% HbC:60% HbA. The

    morphology of the crystals formed was cubic, in contrast with the tetragonal crystals
    MICROSCOPIC

 observed in

    CC and SC disease
    DIAGNOSIS

.

    Early crystals did not exhibit "sharp edges"
    MICROSCOPIC

 until 45 minutes.

    Purified HbKB formed aggregates but not crystals
    MICROSCOPIC

 after 24 hours.

    Isopycnic gradients
    PARACLINICAL

 showed that the

    KB/C compound heterozygotes
    GENETICS

 have

    red blood cell (RBC) densities intermediate between the AC and CC phenotype
    BIOCHEMICAL

 and similar to

    SC disease
    DIAGNOSIS

. The

    surface residue beta 73, known to participate in areas of interaction of the deoxy HbS polymer
    GENETICS

, can now be assigned to areas of contact

    in HbC containing crystals
    MICROSCOPIC

. The

    hemolysis
    BIOCHEMICAL

 observed in the

    HbKB/C compound heterozygote
    GENETICS

 is likely to be secondary to the

    acceleration of Hb crystallization
    BIOCHEMICAL

. The

    microcytosis
    BIOCHEMICAL

 and

    increased RBC density
    MICROSCOPIC

 is clearly the consequence of the presence of

    HbC
    BIOCHEMICAL

, but the basis of the

    increased RBC pathology
    BIOCHEMICAL

 compared with AC trait, despite the

    low proportion of HbC (35% to 40%)
    BIOCHEMICAL

, remains to be elucidated.


When vasculitis is not vasculitis.

Conditions that mask or mimic vascular inflammation are many, the paths to diagnostic distinction are varied, and the prognostic and therapeutic consequences of misreading the signposts are profound. Six cases illustrate.

Conditions that mask or mimic

    vascular inflammation
    SYMPTOMS

 are many, the paths to diagnostic distinction are varied, and the prognostic and therapeutic consequences of

    misreading the signposts
    NEG_FINDINGS

 are profound. Six cases illustrate.


[A case report of atypical Fabry's disease with colon cancer].

An atypical case of Fabry's disease, a rare congenital disorder of glyco-lipid metabolism, associated with sigmoid cancer was reported. A 50-year-old man who had been diagnosed as having atypical form of Fabry's disease complained of lower abdominal pain and difficult defection. A barium enema and an endoscopic examination disclosed sigmoid colon cancer. The cancer was curatively resected. Fabry's disease is often associated with intestinal disease, but the patient with Fabry's disease associated with intestinal malignancy has not been reported.

An atypical case of

    Fabry's disease
    DIAGNOSIS

, a

    rare congenital disorder of glyco-lipid metabolism
    DIAGNOSIS

, associated with

    sigmoid cancer
    DIAGNOSIS

 was reported. A

    50-year-old
    AGE

    man
    GENDER

 who had been diagnosed as having

    atypical form of Fabry's disease
    DIAGNOSIS

 complained of

    lower abdominal pain
    SYMPTOMS

 and

    difficult defection
    SYMPTOMS

. A

    barium enema
    PARACLINICAL

 and an

    endoscopic examination
    PARACLINICAL

 disclosed

    sigmoid colon cancer
    DIAGNOSIS

. The

    cancer
    MEDICATION

 was

    curatively resected
    MEDICATION

.

    Fabry's disease
    DIAGNOSIS

 is often associated with

    intestinal disease
    DIAGNOSIS

, but the patient with

    Fabry's disease associated with intestinal malignancy
    DIAGNOSIS

 has not been reported.

lower abdominal pain
difficult defection


Alpha-galactosidase A deficiency (Fabry's disease) in a black Zimbabwean.

We describe a patient with Fabry's disease with renal and myocardial involvement. He has been followed up for 10 years. This metabolic defect has not been noted before in southern Africa; the clinical course is similar to that of western European and American cases.

We describe a patient with

    Fabry's disease
    DIAGNOSIS

 with

    renal and myocardial involvement
    SYMPTOMS

.

    He
    GENDER

 has been followed up for 10 years. This

    metabolic defect
    DIAGNOSIS

 has not been noted before in

    southern Africa
    ETHNICITY

; the clinical course is similar to that of

    western European
    ETHNICITY

 and American cases.


Angiokeratoma corporis diffusum with glycopeptiduria due to deficient lysosomal alpha-N-acetylgalactosaminidase activity. Clinical, morphologic, and biochemical studies.

Angiokeratoma corporis diffusum is a prominent cutaneous feature of certain lysosomal storage diseases. In this article, the clinical, morphologic, and biochemical features of a new, adult-onset lysosomal disease with angiokeratoma are described.

A 46-year-old Japanese woman had diffuse angiokeratoma, mild intellectual impairment, and peripheral neuroaxonal degeneration. The angiokeratoma first appeared on her lower torso when she was 28 years old, and then it became diffusely distributed. Histopathologically, the telangiectasia had localized hyperkeratosis; ultrastructural examination revealed clear cytoplasmic vacuoles in all dermal cells, particularly in vascular and lymphatic endothelial cells and in eccrine sweat gland cells. The lysosomal pathologic features and increased urinary excretion of O-linked glycopeptides suggested the deficiency of a specific glycosidase. Enzyme analyses revealed less than 2% of normal alpha-N-acetylgalactosaminidase activity and the absence of immunodetectable enzyme protein. Her two unaffected children had half-normal alpha-N-acetylgalactosaminidase levels, consistent with the autosomal recessive inheritance of the enzymatic defect.

Since this enzyme deficiency was previously identified in patients with an infantile form of inherited neuroaxonal dystrophy, the occurrence of the enzymopathy in the 46-year-old proband described herein represents an adult-onset form of alpha-N-acetylgalactosaminidase deficiency. This newly recognized entity should be considered in the differential diagnosis of angiokeratoma corporis diffusum.

    Angiokeratoma corporis diffusum
    SYMPTOMS

 is a prominent cutaneous feature of certain

    lysosomal storage diseases
    DIAGNOSIS

. In this article, the clinical, morphologic, and biochemical features of a new,

    adult-onset lysosomal disease
    AGE

 with

    angiokeratoma
    SYMPTOMS

 are described.

A

    46-year-old
    AGE

    Japanese
    ETHNICITY

    woman
    GENDER

 had

    diffuse angiokeratoma
    SYMPTOMS

,

    mild intellectual impairment
    SYMPTOMS

, and

    peripheral neuroaxonal degeneration
    SYMPTOMS

. The

    angiokeratoma
    SYMPTOMS

 first appeared

    on her lower torso
    SYMPTOMS

 when

    she
    GENDER

    was 28 years old
    AGE

, and then it became

    diffusely distributed
    SYMPTOMS

. Histopathologically, the

    telangiectasia
    MICROSCOPIC

 had

    localized hyperkeratosis
    MICROSCOPIC

;

    ultrastructural examination
    PARACLINICAL

 revealed

    clear cytoplasmic vacuoles in all dermal cells, particularly in vascular and lymphatic endothelial cells and in eccrine sweat gland cells
    MICROSCOPIC

. The

    lysosomal pathologic features
    MICROSCOPIC

 and

    increased urinary excretion of O-linked glycopeptides
    BIOCHEMICAL

 suggested the

    deficiency of a specific glycosidase
    BIOCHEMICAL

.

    Enzyme analyses
    PARACLINICAL

 revealed

    less than 2% of normal alpha-N-acetylgalactosaminidase activity
    BIOCHEMICAL

 and the

    absence of immunodetectable enzyme protein
    BIOCHEMICAL

.

    Her
    GENDER

    two unaffected children had half-normal alpha-N-acetylgalactosaminidase levels
    FAMILY

, consistent with the

    autosomal recessive inheritance of the enzymatic defect
    GENETICS

.

Since this

    enzyme deficiency
    BIOCHEMICAL

 was previously identified in patients with an

    infantile form of inherited neuroaxonal dystrophy
    DIAGNOSIS

, the occurrence of the

    enzymopathy
    DIAGNOSIS

 in the

    46-year-old
    AGE

    proband
    GENDER

 described herein represents an

    adult-onset
    AGE

 form of

    alpha-N-acetylgalactosaminidase deficiency
    BIOCHEMICAL

. This newly recognized entity should be considered in the

    differential diagnosis
    PARACLINICAL

 of

    angiokeratoma corporis diffusum
    SYMPTOMS

.

Angiokeratoma corporis diffusum
angiokeratoma
diffuse angiokeratoma
mild intellectual impairment
peripheral neuroaxonal degeneration
angiokeratoma
on her lower torso
diffusely distributed
angiokeratoma corporis diffusum


Angiokeratomas in Fabry's disease and Fordyce's disease: successful treatment with copper vapour laser.

Two patients with multiple angiokeratomas on genitalia and thighs, one with Fabry's disease and one with Fordyce's disease, were treated with copper vapour laser light of 578 nm wavelength. The result was desirable, with destruction and disappearance of the lesions and minimal scarring and posttreatment hyper- or hypopigmentation.

Two patients with

    multiple angiokeratomas on genitalia and thighs
    SYMPTOMS

, one with

    Fabry's disease
    DIAGNOSIS

 and one with

    Fordyce's disease
    DIAGNOSIS

, were treated with

    copper vapour laser light of 578 nm wavelength
    MEDICATION

. The result was desirable, with

    destruction and disappearance of the lesions
    SYMPTOMS

 and

    minimal scarring
    SYMPTOMS

 and

    posttreatment hyper- or hypopigmentation
    SYMPTOMS

.


New findings in pathology of storage.

New clinicopathological phenotypes are described in this report. A subclinical form of cholesterol ester storage disease was diagnosed in two adult female patients with hyperlipoproteinaemia type IIb. Both were profoundly deficient in acid lipase activity. Fabry's disease was described with intensive storage of globotriaosyl ceramide restricted solely to the heart muscle which was enormously hypertrophic. The clinical course resembled that of idiopathic hypertrophic cardiomyopathy. The variants of sphingomyelinase deficiency type A described previously are reviewed and their clinical course revised. Two of the three patients with the minimal neurological lesion still display, after a four year interval, a stable course (ages 7 and 14 years) while the neurological status of the third one (aged 8 years) deteriorated profoundly. The clinical condition of the two cases with protracted neurovisceral symptomatology (aged now 29 and half, and 30 years) is unchanged.

New clinicopathological phenotypes are described in this report. A

    subclinical form of cholesterol ester storage disease
    DIAGNOSIS

 was diagnosed in two

    adult
    AGE

    female
    GENDER

 patients with

    hyperlipoproteinaemia type IIb
    DIAGNOSIS

. Both were

    profoundly deficient in acid lipase activity
    BIOCHEMICAL

.

    Fabry's disease
    DIAGNOSIS

 was described with

    intensive storage of globotriaosyl ceramide restricted solely to the heart muscle which was enormously hypertrophic
    MICROSCOPIC

. The clinical course resembled that of

    idiopathic hypertrophic cardiomyopathy
    DIAGNOSIS

. The variants of

    sphingomyelinase deficiency type A
    BIOCHEMICAL

 described previously are reviewed and their clinical course revised. Two of the three patients with the

    minimal neurological lesion
    SYMPTOMS

 still display, after a four year interval, a

    stable course
    SYMPTOMS

 (

    ages 7 and 14 years)
    AGE

 while the

    neurological status
    SYMPTOMS

 of the third one (

    aged 8 years
    AGE

)

    deteriorated profoundly
    SYMPTOMS

. The clinical condition of the two cases with

    protracted neurovisceral symptomatology
    SYMPTOMS

 (

    aged now 29 and half, and 30 years
    AGE

) is unchanged.

minimal neurological lesion
stable course
neurological status
deteriorated profoundly
protracted neurovisceral symptomatology


Avascular necrosis of the carpal scaphoid: Preiser's disease: report of 6 cases and review of the literature.

Six cases of nontraumatic avascular necrosis of the scaphoid are reported. Two cases were due to chronic steroid intake with several other sites of bone necrosis; for the other 4 cases no etiology could be established. Four were treated with a proximal row carpectomy, 3 with a very satisfying result, whereas one had to be converted into a wrist arthrodesis.

Six cases of

    nontraumatic avascular necrosis of the scaphoid
    DIAGNOSIS

 are reported. Two cases were due to

    chronic steroid intake
    MEDICATION

 with

    several other sites of bone necrosis
    SYMPTOMS

; for the other 4 cases

    no etiology could be established
    NEG_FINDINGS

. Four were treated with a

    proximal row carpectomy
    MEDICATION

, 3 with a very satisfying result, whereas one

    had to be converted into a wrist arthrodesis
    MEDICATION

.


Fabry's disease: heterozygous form of different expression in two monozygous twin sisters.

A 26-year-old woman presented widespread angiokeratomas predominantly in a swimsuit distribution pattern associated with acroparesthesia in all four limbs. The tentative diagnosis of Fabry's disease (FD) was confirmed by optical and electron-microscopic findings and by appropriate biochemical testing. The work-up showed ocular and renal manifestations of the disease. The monozygous twin sister of the patient was asymptomatic although she was shown to be heterozygous for the enzymatic defect. These 2 cases illustrate the concept of extreme lyonization which can explain observed phenotypic differences in heterozygous females with X-linked hereditary diseases. The father and mother of the patient were shown to be noncarriers of the trait, suggesting de novo mutation in the twin pregnancy. However, biochemical testing for the detection of FD heterozygous females cannot rule out the possibility of the mother being heterozygous with normal enzyme activity.

A

    26-year-old
    AGE

    woman
    GENDER

 presented

    widespread angiokeratomas predominantly in a swimsuit distribution pattern
    SYMPTOMS

 associated with

    acroparesthesia in all four limbs
    SYMPTOMS

. The tentative diagnosis of

    Fabry's disease (FD)
    DIAGNOSIS

 was confirmed by

    optical and electron-microscopic findings
    PARACLINICAL

 and by appropriate

    biochemical testing
    PARACLINICAL

. The

    work-up
    PARACLINICAL

 showed

    ocular and renal manifestations of the disease
    SYMPTOMS

.

    The monozygous twin sister of the patient was asymptomatic
    FAMILY

 although

    she
    GENDER

    was shown to be heterozygous for the enzymatic defect
    FAMILY

. These 2 cases illustrate the concept of extreme lyonization which can explain observed phenotypic differences in

    heterozygous
    GENETICS

    females
    GENDER

 with

    X-linked hereditary diseases
    GENETICS

.

    The father and mother of the patient were shown to be noncarriers of the trait, suggesting de novo mutation in the twin pregnancy
    FAMILY

. However,

    biochemical testing
    PARACLINICAL

 for the detection of

    FD
    DIAGNOSIS

 heterozygous

    females
    GENDER

 cannot rule out the possibility of the

    mother being heterozygous with normal enzyme activity
    FAMILY

.

heterozygous
X-linked hereditary diseases