Fabry disease: detection of heterozygotes by examination of glycolipids in urinary sediment.

Fabry disease is an X-linked sphingolipid disorder that is manifest clinically as a disease of nerves, kidneys, and blood vessels. Precise identification of Fabry heterozygotes is essential for genetic counseling. Heterozygote detection by enzyme assay does not consistently distinguish them from unaffected females. We describe a method for Fabry heterozygote detection, based on quantitation of urinary sediment glycolipids by high-performance liquid chromatography. In specimens from 12 Fabry heterozygotes, the total glycolipid fraction was increased (10 to 100-fold) and trihexosyl ceramide (CTH) was 2- to 70-fold times normal. Digalactosyl ceramide (Digal-Cer), which is normally present in trace amounts in urine, was also increased. The ratio of CTH and Digal-Cer to hydroxy fatty acid glucosyl ceramide was increased and seemed to be characteristic of Fabry disease. This method provides rapid and accurate detection of Fabry heterozygotes.