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Genetic heterogeneity of α‐galactosidase in fabry's disease
Author(s) -
Romeo Giovanni,
Childs Barton,
Migeon Barbara R.
Publication year - 1972
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(72)80432-0
Subject(s) - medicine , medical school , medical genetics , gerontology , family medicine , pediatrics , genetics , medical education , biology , gene
Fabry’s disease in an X-linked disorder characterized by the abnormal accumulation of a neutral glycolipid, trihexosylceramide (galactosylgalactosylglucosylceramide) [ 11. The clinical manifestations include a vascular rash of the skin, febrile crises, and severe pain in the extremities. The deficient enzyme is the one which cleaves the glycosidic bond between the terminal and pre-terminal galactose residues of trihexosylceramide [2]. A deficiency of ol-galactosidase (EC 3.2.1. 22), assayed with the synthetic substrates p-nitrophenyl a-galactopyranoside and 4-methylumbelliferyl a-galactopyranoside, has been found in leukocytes [3] and skin tibroblasts [4, 51 of patients. Heterozygotes have two clonal populations of fibroblasts, one with a-galactosidase activity similar to controls and the other with activity in the range of patients [4]. The specificity of the assay for a-galactosidase, based on the use of synthetic substrates, has been questioned [6,7] because it was thought that the terminal glycosidic bond of the natural substrate had a p-anomeric configuration, but recent studies have shown the terminal galactose of trihexosylceramide to be an ol-anomer [8-l 11. However, the enzymatic assay based on the use of synthetic substrates might measure the activity of more than one cr-galactosidase and, indeed, two forms of the enzyme have been partially purified and characterized from human kidney