Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002986 (Fabry)
 5,646 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three unrelated men with Fabry's disease (angiokeratoma corporis diffusum universale) and accelerated atrioventricular conduction are described. AQn His bundle electrogram in one patient who reported episodes of tachycardia demonstrated a prolonged deflection preceding the ventricular complex. This deflection is thought to represent an abnormal His bundle potential, possible resulting from glycolipid deposition. In the second patient the PR interval decreased from 0.18 to 0.11 second during 10 years, and in the third patient it decreased from 0.12 to 0.10 seconds during 13 years. Accelerated atrioventricular conduction may develop in Fabry's disease.
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PMID:Accelerated atrioventricular conduction in Fabry's disease: a case report. 9 64

Fabry's disease has been reported to be associated with ECG abnormalities. Thirty-two patients with this disease followed in the University of Minnesota had ECG's and 15 had VCG's. An abonrmal rhythm was observed in two patients on initial examination and four more developed abnormal rhythm on follow-up examinations. A short PR interval (120 msec. or less) was seen in five patients. Thirteen others had a PR interval that was less than 140 msec. Conduction abnormalities involving the A-V node or His bundle or its branches were present in 22 per cent of the patients, most frequently the intraventricular conduction defects progressing to the right bundle branch block. Atrial or ventricular enlargement was seen in 60 per cent of the patients, left ventricular hypertrophy being the most common. ST-T changes with or without chamber enlargement were seen in 10 patients. One patient had an anterior myocardial infarction pattern on his ECG. Hemizygosity was found to be associated with significantly more abnormalities than heterozygosity. The severity of conduction defects also increased with the duration of the disease process. Vectorcardiography in this study did not provide significant additional information other than that observed on the ECG alone. Since the pathology usually reveals myocardial fibers, conduction system, and blood vessels infiltrated with glycosphingolipid, it is believed that lipid infiltration is responsible for conduction defects, chanber enlargement, and other abnormalities. Although Fabry's disease is rate, it may be amenable to therapy; therefore, recognition of cardiac involvement is important.
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PMID:Electrocardiographic and vectorcardiographic abnormalities in Fabry's disease. 14 May 98

A family is described in which a 33-year-old man has classic X-linked recessive Fabry disease. His 2 sisters were discovered to be heterozygous carriers of the Fabry gene and to have both episodic and permanent neurological deficits including vertigo, tinnitus, long tract motor signs, and bladder incontinence. The most concise explanation for these findings is that the sisters manifest central nervous system complications of the Fabry carrier state. This family provides additional evidence that female carriers of rare X-linked recessive disorders may exhibit serious consequences of the disease, presumably related to tissue variability in expression of mutant enzyme activity.
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PMID:Neurological manifestations of Fabry disease in female carriers. 21 99

A 46-year-old man with Fabry's disease having aortic regurgitation and complete atrioventricular (AV) block was presented. In spite of severe aortic regurgitation (Seller's grade 3/4), his two-dimensional (2-D) echocardiogram revealed increased thickness of the left ventricular wall with mild dilatation. The myocardial echo showed a fine granular sparkling texture suggesting phospholipid deposition in the myocardial tissue. The membranous portion of the interventricular septum was thickened, and the aortic valve was thickened and had imperfect coaptation. Endomyocardial biopsy of the right side of the interventricular septum revealed intramyocardial vacuolization by light microscopy. Electron microscopy confirmed the presence of myelinoid lamellar inclusion. Electrophysiologic examination revealed an intra-Hissian AV block. A DDD pacemaker was implanted and the patient's symptoms were improved. Valvular replacement was not attempted due to the danger of suture failure. The patient's brother (41-year-old) also had increased thickness of his left ventricular wall on echocardiography, and a complete AV block by ECG, but no valvular abnormalities. His sister (45-year-old) had increased thickness of the left ventricular wall on echocardiography, and negative T waves by ECG, but she had no cardiac symptoms. The possibility of cardiac involvement in this heterozygous woman with Fabry's disease should also be considered. The patient's 38-year-old sister and all the children of all family members had normal left ventricular wall thicknesses and normal ECG. These findings may correspond to the age-related disease severity. The possibility of cardiac abnormalities should be considered in heterozygous women with Fabry's disease.
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PMID:[Echocardiographic findings in a case of Fabry's disease with aortic regurgitation and complete AV block, and in his family members]. 315 Apr 46

The present case is a 24-years-old man who complained painful attack with numbness in both bilateral shoulder regions and distal extremities. This pain was increased by the stimulations of sunlight and heat. On physical examinations, he had an acromegalic-like-appearance, thick mustache and beard. Malocclusion of the teeth which showed the broad space was found. And skin lesion was not found out. Hypesthesia in bilateral distal extremities was revealed and no other abnormal neurological findings were observed. He was made diagnosis of Fabry's disease by laboratory examinations which were alpha-galactosidase deficiency analysed in leukocytes, increased ceramide trihexosides demonstrated in urinary sediment and electron microscopic findings in the biopsy of the skin and sural nerve. His mother had and decreased alpha-galactosidase activity which levels showed between normal and patient and was speculated to be a carrier. On an electron microscopy, "Zebra body" was observed in fibroblasts, capillary endothelial cells, their pericytes, prineural and Schwann cells. Many of them had a distinct limiting membrane and laminal structure with irregular alterations of light and dark zone. In the cytoplasma of Schwann cells, there were many rough endoplasmic reticulums which were located parallel with alignment and seemed to show the loosed laminal structure with the unclear limited membrane. Occasionally, fusions between irregular laminal structure and rough endoplasmic reticulum were also observed. These findings could be indicated that the formation of Zebra body is related to rough endoplasmic reticulum, because laminal structure which described above is corresponded to pre-Zebra body. In the cytoplasma of the prineural cells, recket-like structure which was seen in histiocytosis X were occasionally observed.
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PMID:[Fabry's disease with malocclusion and acromegalic-appearance: clinical and electromicroscopic studies (author's transl)]. 624 68

Apparent deficiency of alpha-galactosidase A was observed in a 51-year-old, clinically healthy male, with no clinical symptoms of Fabry disease, and without excess urinary excretion of ceramide trihexoside. The deficiency, which was similar to that found in Fabry disease patients, could be demonstrated using both synthetic and natural substrates. This pseudodeficiency was transmitted in his family by classical X-linked inheritance. His wife showed enzyme activity in the normal range, two daughters were heterozygotes for this mutation as demonstrated by hair root assay, and three sons showed normal alpha-galactosidase activity. Kinetic studies in cultured skin fibroblasts indicated a five-fold increase in the apparent Km and a greater heat stability of the residual alpha-galactosidase activity when compared to controls. These data indicate that the residual enzyme activity in this mutation behaves similarly to that observed in Fabry disease patients but does not cause any clinical abnormalities.
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PMID:Pseudodeficiency of alpha-galactosidase A. 627 39

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.
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PMID:Painful fingers, heat intolerance, and telangiectases of the ear: easily ignored childhood signs of Fabry disease. 750 49

Both Fabry disease and Duchenne muscular dystrophy were confirmed by gene analysis in a Japanese boy. He developed muscle weakness at 4 years of age. A muscle biopsy revealed lamellar inclusion bodies in vascular endothelial cells in addition to myopathic changes with negative dystrophin staining. The myopathic symptoms progressed, and he died of pneumonia at 24 years of age. No clinical manifestations of Fabry disease were observed except for hypohidrosis and angiokeratoma. However, glycolipid accumulation was found in biopsied renal tissue. Molecular analysis demonstrated two gene mutations; a novel single-base deletion in exon 3 of the alpha-galactosidase gene, and a dystrophin gene deletion extending from exon 46 to exon 50. His mother was confirmed to be heterozygous for both gene deletions.
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PMID:Coexistence of gene mutations causing Fabry disease and Duchenne muscular dystrophy in a Japanese boy. 883 34

A male patient presented with oligosymptomatic Fabry disease (end stage renal failure and non-obstructive cardiomyopathy) at around 30 years of age. His leukocyte alpha-galactosidase activity (alpha-gal) was 2.6% of controls. A 50-year-old sister had similar cardiac symptoms and her asymptomatic heterozygous daughter (33 years) had normal enzyme activity. All three patients carried a novel, 6bp insertion on exon 7 of the AGAL gene. The majority of male Fabry patients carrying mutations in exon 7 have residual alpha-gal below 1% and suffer from neuropathic pain. Comparable oligosymptomatic phenotypes in Caucasian patients carry a common mutation on exon 6 (R301Q) and have a significantly later onset. The course of the disease is likely to be altered by recombinant enzyme therapy in the future. Therefore, a thorough documentation of phenotypes, residual activities and underlying genotypes is of current interest.
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PMID:A novel 6 bp insertion in exon 7 associated with an unusual phenotype in a family with Fabry disease. 1270 99

A 65-year-old man presented to our institution for workup of proteinuria. His serum creatinine level was 1.7 mg/dL (130 micromol/L), and he had proteinuria with protein of almost 5 g/24 h. Fabry disease was diagnosed by means of kidney biopsy and low serum and leukocyte levels of alpha-galactosidase A. Review of his history, family history, physical examinations, and diagnostic studies did not show other findings typical of this disease. His renal function continued to decline, and he eventually underwent a living unrelated renal transplantation 5 years later. Three years after transplantation, his creatinine level is 1.7 mg/dL (130 micromol/L), and corrected iothalamate clearance is 53 mL/min/1.73 m2 . Genetic studies showed that he has a novel missense mutation (M42L) in exon 1. Methionine at codon 42 is highly conserved in eukaryotic alpha-galactosidase A orthologues. This genotype predicts a minor misfolding of alpha-galactosidase A because of a small difference in hydrophobicity between methionine and leucine. His mutation resulted in a very low, but detectable, serum level of alpha-galactosidase A (0.002 U/L; normal range, 0.016 to 0.2 U/L). Cases of Fabry disease that present with predominantly renal manifestations are rare and require a high index of suspicion for diagnosis. Because treatment for Fabry disease recently has become available, it is important for clinicians to be aware of this disease and pursue the diagnosis in cases of otherwise unexplained renal dysfunction.
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PMID:A novel alpha-galactosidase a mutant (M42L) identified in a renal variant of Fabry disease. 1549 42


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