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)

A Fabry heterozygote with early clinical manifestations of this X linked disorder is described. Her symptoms, including febrile attacks, arthralgia, abdominal pain, and neurological signs, were characteristic of Fabry's disease hemizygotes. The neurological findings were compatible with a brain stem infarction. The diagnosis was confirmed by the finding of low activities of alpha-galactosidase A (alpha-galA) in plasma, lymphocytes, and cultured fibroblasts, and by the observation of typical lamellar inclusions in the lysosomes of cultured fibroblasts. Increased levels of ceramide trihexoside were also found by TLC of urine sediment. The family history gave no indication of Fabry's disease in the patient's relatives, and biochemical and ultrastructural investigations of their cells were also normal. Our findings therefore suggest that the defective gene in the heterozygote has resulted from a new mutation.
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PMID:A Fabry's disease heterozygote with a new mutation: biochemical, ultrastructural, and clinical investigations. 216 29

Globotriaosylceramide, the natural substrate of alpha-galactosidase A (the enzyme deficient in Fabry's disease) was prepared from human kidney by repeated medium pressure chromatography on Lichroprep Si 60 (E. Merck) before and after peracetylation. The apparently homogeneous preparation migrating as a single band on HPTLC was analysed by fast atom bombardment mass spectrometry and 1H-NMR at 500 MHz. It was found that in this fraction two major molecular species were comigrating: Gal alpha 1-4Gal beta 1-4Glc beta 1-1ceramide with nervonic and lignoceric acid linked to phytosphingosine and Gal beta 1-4Glc beta 1-1 ceramide with palmitic acid linked to sphingosine.
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PMID:The determination of phytosphingosine-containing globotriaosylceramide from human kidney in the presence of lactosylceramide. 216 61

We identified a structural defect of alpha-galactosidase A (alpha-Gal A) gene in a Japanese patient with Fabry disease. A partial deletion approximately 0.4 kilobase-pairs in size was delineated by restriction endonuclease mapping; whole exon 3 sequence was removed. alpha-Gal A mRNA was deficient in the mRNA preparation from the lymphoblastoid cells derived from the patient, and a faulty transcription resulting in an unstable alpha-Gal A message was suggested in this case. Molecular pedigree analysis was successfully performed in identifying heterozygotes and the ancestry of the mutant allele in this family.
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PMID:[Partial deletion of alpha-galactosidase A gene in a Japanese mutant of Fabry disease]. 216 64

Fabry's disease, which is characterized by alpha-galactosidase A (AG) deficiency, causes early renal failure. Kidney transplants do not reliably supply the deficient enzyme. To assess both urinary excretion of AG by the transplant and the relationship between urine and serum hydrolase activity, acute and chronic acid-base studies were performed in normal control subjects and in the patient with Fabry's disease who had undergone renal transplantation. For the acute studies, alkalosis was induced by intravenous infusion of sodium bicarbonate and acidosis was induced by ingestion of ammonium chloride. The chronic study involved long-term ingestion of NH4Cl by only the patient with Fabry's disease. The results show that AG is secreted by the renal graft. Urinary hydrolase excretion was increased by acute alkalinization and decreased by acute acidification. Acute, but not chronic, acidification increased the patient's serum AG activity, indicating that long-term acidification is not useful for treating Fabry's disease after transplantation. The large changes in hydrolyase excretion induced by acute and chronic acid-base changes show the difficulty of using lysosomal enzymuria as a diagnostic marker for renal disorders without knowledge of acid-base conditions.
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PMID:Effect of acid-base changes on urinary hydrolases in Fabry's disease after renal transplantation. 216 77

A partial deletion involving exon 3 associated with a single base change (A to C) was found in the alpha-galactosidase A gene of a hemizygous male Fabry patient and his mother, a heterozygous proband. This 402-bp deletion was flanked by 6-bp direct repeat sequences, and the intervening portion was found to have unique complementary sequences. These specific structures may have promoted "slipped mispairing" in this family.
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PMID:Partial deletion of human alpha-galactosidase A gene in Fabry disease: direct repeat sequences as a possible cause of slipped mispairing. 216 7

Anderson-Fabry disease is an X-linked inborn error of metabolism characterized by subnormal activity of the lysosomal hydrolase, alpha-galactosidase A. We have assessed the incidence and nature of neuropathy in 12 patients (seven affected men and five carrier females). Abnormalities of cutaneous thermal sensation were common, even in asymptomatic carriers, with a unique predilection for cold sensitivity which suggests involvement of small myelinated nerve fibres. Intracranial abnormalities were frequently detected by magnetic resonance imaging (MRI) in males, both with and without overt cerebrovascular disease, and were more extensive in older patients. Such abnormalities were not detected in carriers. Auditory and vestibular abnormalities were present in six patients, only one of whom was symptomatic. Cranial MRI and assessment of cutaneous thermal thresholds are sensitive techniques which can identify neurological involvement in asymptomatic patients. They may be of benefit in monitoring the effectiveness of enzyme replacement therapy and excluding the carrier state for the defective gene.
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PMID:The neurological complications of Anderson-Fabry disease (alpha-galactosidase A deficiency)--investigation of symptomatic and presymptomatic patients. 216 95

Efforts were directed to identify the specific mutations in the alpha-galactosidase A (alpha-Gal A) gene which cause Fabry disease in families of Japanese origin. By polymerase-chain-reaction-amplification of DNA from reverse-transcribed mRNA and genomic DNA, different point mutations were found in two unrelated Fabry hemizygotes. A hemizygote with classic disease manifestations and no detectable alpha-Gal A activity had a G-to-A transition in exon 1 (codon 44) which substituted a termination codon (TAG) for a tryptophan codon (TGG) and created an NheI restriction site. This point mutation would predict a truncated alpha-Gal A polypeptide, consistent with the observed absence of enzymatic activity and a classic Fabry phenotype. In an unrelated Japanese hemizygote who had an atypical clinical course characterized by late-onset cardiac involvement and significant residual alpha-Gal activity, a G-to-A transition in exon 6 (codon 301) resulted in the replacement of a glutamine for an arginine residue. This amino acid substitution apparently altered the properties of the enzyme such that sufficient enzymatic activity was retained to markedly alter the disease course. Identification of these mutations permitted accurate molecular heterozygote diagnosis in these families.
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PMID:Identification of point mutations in the alpha-galactosidase A gene in classical and atypical hemizygotes with Fabry disease. 217 31

A 39 year-old man was found to have mild proteinuria by urinary examination since one year ago. He was for the first time diagnosed as having Fabry's disease by histopathological and electronmicroscopic findings of the renal biopsy specimens, which showed the presence of numerous vacuolated cells and electron dense bodies inside the cells. The level of WBC alpha-galactosidase was significantly lower than normal level. The pedigree of this patient showed a familial history of various types of renal disease. One of the patient's brothers also showed decreased level of WBC alpha-galactosidase, who has been treated by maintenance hemodialysis for 2 years. It is concluded that early diagnosis of this disease through renal biopsy and WBC alpha-galactosidase level is important to manage the future course of patients with Fabry's disease.
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PMID:[A case of Fabry's disease detected by renal biopsy findings]. 217 29

Endocytotic internalization of alpha-galactosidase by cultured fibroblasts derived from a patient with Fabry's disease was achieved via receptor-mediated endocytosis of alpha-2-macroglobulin (alpha-2-M). alpha-galactosidase of coffee beans was conjugated to alpha-2-M when the latter was treated with trypsin. Internalization of the conjugate resulted in an increase of alpha-galactosidase activity in the crude cell extracts. The observed internalization was blocked by the presence of bacitracin, an inhibitor of binding between alpha-2-M and its receptor on the cell surface. When the cells were incubated at 4 degrees C with the conjugate, internalization was also inhibited. The alpha-galactosidase activity in the cells was saturated when the concentration of the conjugate in the medium was 40 micrograms/ml. Since non-conjugated alpha-galactosidase was not effectively internalized, the observed internalization of the conjugate was mediated by recognition of alpha-2-M by its receptor. The effective internalization of alpha-galactosidase described in this paper has a potential use in the enzyme replacement therapy of Fabry's disease.
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PMID:Endocytotic internalization of alpha-2-macroglobulin: alpha-galactosidase conjugate by cultured fibroblasts derived from Fabry hemizygote. 243 88

In our previous report we described the endocytotic incorporation of coffee bean alpha-galactosidase conjugated to human alpha-2-macroglobulin (alpha-2-M) into cultured fibroblasts derived from a patient with Fabry's disease (1). The fate of internalized alpha-galactosidase according to the method described in the above report is now studied. Measurement of the enzyme activity of subcellular fractions showed that it was concentrated in the lysosomal-mitochondrial fraction. The half-life of internalized alpha-galactosidase was determined to be 2 h.
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PMID:The fate of internalized alpha-2-macroglobulin: alpha-galactosidase conjugate in fibroblasts from Fabry's hemizygote. 243 20


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