title: Metabolism of ceramide trihexoside in cultured skin fibroblasts from Fabry's patients, carriers and normal controls.
abstract: The metabolism of ceramide trihexoside (CTH) was studied in cultured skin fibroblasts from Fabry's patients, carriers, and controls. The in vitro activities of alpha-galactosidase in fibroblasts using either artificial substrate or CTH led to a clear identification of 4 Fabry's patients, 6 carriers and 8 controls. Normal findings were noted in one carrier. In fibroblasts from Fabry's patients, the residual activities assayed with CTH were less than those with the artificial substrate. In the CTH-loading test, the incorporation and hydrolysis of CTH in the fibroblasts were closely related with the culture time and CTH-concentration in the medium. With 0.5 nmol CTH per flask (25 cm2 growth area, 3 ml of medium), the hydrolysis rate of CTH, based on its incorporation, was 2.1% in fibroblasts from 4 Fabry's patients, 82.0% in 10 controls and 47.1% in 6 out of 7 carriers on the 7th day of culture. The impaired hydrolysis in carriers' fibroblasts differs from the hydrolysis noted in fibroblasts from carriers of autosomal recessive sphingolipidoses with a normal hydrolysis. These findings explain that some of the carriers show clinical symptoms and a mild accumulation of CTH in their tissues, such as seen in Fabry's patients. In one carrier there was a normal hydrolysis of CTH, both in vitro and in the CTH-loading study. This may be explained by Lyon's random X-chromosome inactivation theory.
mesh_terms: D002478:Cells, Cultured; D000795:Fabry Disease / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006580:Genetic Carrier Screening; D006028:Glycosphingolipids / Q000378:metabolism*; D006801:Humans; D008297:Male; D012867:Skin / Q000378:metabolism; D014281:Trihexosylceramides / Q000378:metabolism*; D000519:alpha-Galactosidase / Q000378:metabolism
chemical_list: D006028:Glycosphingolipids; D014281:Trihexosylceramides; D000519:alpha-Galactosidase