Fabry's disease: enzymatic diagnosis of hemizygotes and heterozygotes. Alpha-galactosidase activities in plasma, serum, urine, and leukocytes.

Abstract Fabry's disease is an X-linked, inborn error of glycosphingolipid metabolism resulting from the deficient activity of the enzyme, ceramide trihexosidase, a specific α-galactosidase. A sensitive, simple enzymatic assay was developed to measure α-galactosidase activity in plasma, serum, urine, and leukocytes; the demonstration of deficient α-galactosidase activity in these sources, utilizing synthetic fluorogenic substrate, proved to be diagnostic for hemizygotes and heterozygotes with Fabry's disease. The pH optima was the same for heterozygotes and normal control subjects for each enzyme source. Typical saturation kinetics were observed in all enzyme sources from all individuals studied. The apparent Km values were similar in respective enzyme sources from a hemizygote, heterozygote, and normal control subjects. Enzymatic activity measured in hemizygotes was approximately 10 per cent of normal nonspecific α-galactosidase activity in leukocytes, plasma, serum, and urine. Heat inactivation studies of the enzyme in leukocytes and plasma from hemizygotes, heterozygotes, and normal individuals indicated the presence of heat-stable and heat-labile components of α-galactosidase activity; these studies suggest that the residual α-galactosidase activity in hemizygotes with this disease is a heat-stable component and that the deficient enzyme in Fabry's disease, ceramide trihexosidase, is the heat-labile, myoinositol-inhibited α-galactosidase component.