PITEVNÍ DIAGNÓZA FABRYHO NEMOCIU HETEROZYGOTKY, VEDOUCÍ K ROZPOZNÁNÍNEDIAGNOSTIKOVANÉ MANIFESTNÍ NEMOCI V RODINĚ

Post-mortem Diagnosis of Fabry’s Disease in a Female Hetero-zygote Leading to the Recognition of Undiagnosed Manifest Disease in the Family

The authors detected on necropsy in a 63-year-old woman with the clinical diagnosis of hypertension, atheroscle-rosis of the coronary and peripheral arteries, thromboembolism into the cerebral circulation and impaired cardiacconductivity lysosomal storage identified by histochemical and electronoptic analyses along with lipid chromatog-raphy as Fabry’s disease. The stored lipids were neutral glycosphingolipids of the globo series globotriaosylceramide)and of the gala- series (galabiosylceramide) which accumulated as a result of deficient activity of the degradingenzyme alpha galactosidase A. Marked accumulation of these specific lipids was found in cardiomyocytes, in smoothmuscles (of the media in arteries of the heart, kidneys, liver, spleen, lungs) in podocytes and mesangial cells of renalglomeruli, in epithelia of Henle’s loop and in the distal tubules. In the vascular endothelium the storage was at theborderline of detectability. Accumulation did not lead to detectable organ disorders with the exception of the heartwhere it participated, no doubt, significantly in the cardiocyte hypertrophy. Examination of relatives revealed in theproband’s son (age 41 years) a combination of renal, cardiac and skin changes typical for Fabry’s disease which,however was not clinically diagnosed. The diagnosis was confirmed by proving of alpha-galactosidase A deficiencyin the peripheral leucocytes and point mutation L293X in the VIth exon of the appropriate gene. In a granddaughter(age 15 years) biochemical and molecular genetic methods revealed the heterozygous state of Fabry’s disease inpreclinical stage.

Key words:
Fabry’s disease, cardiomyopathy, alpha galactosidase deficiency, manifest heterozygous condition.