Diagnosis of Glycosphingolipidoses by Urinary-Sediment Analysis

Biochemical diagnosis of patients with Krabbe's leukodystrophy, Gaucher's disease, lactosylceramidosis, Fabry's disease, Sandhoff's disease and metachromatic leukodystrophy can be made by the chemical analysis of urinary sediment from a 24-hour collection. Individual neutral glycosphingolipids were separated by thin-layer chromatography and quantitatively estimated by gas-liquid chromatography Marked accumulation of the characteristic glycosphingolipid was found in the sediment from patients with these diseases whereas normal sediment contained only small amounts of glycolipid material. With this method it was possible to detect genetic variants of Fabry's disease and heterozygotes for both Fabry's and Gaucher's diseases. DURING the past decade, notable advances have been made in the understanding of the biochemistry and pathophysiology of glycosphingolipidoses.¹ With the recent identification of the specific enzymatic defects in Krabbe's leukodystrophy,²,³ lactosylceramidosis ⁴ and Sandhoff's disease,⁵ knowledge of the primary defects in the inborn errors of glycosphingolipid catabolism has increased. Table 1 summarizes the glycosphingolipidoses, their respective enzymatic defects and the characteristic accumulating glycosphingolipids.^{6 7 8 9 10 11 12 13} These glycosphingolipids share a common structure called ceramide (Cer, 2-N-acylsphingosine), which is the hydrophobic part of the molecule. The glycosyl unit of varying length and polarity is attached to the ceramide moiety by a glycosidic bond between.