Demonstration of a deficiency of glucocerebroside-cleaving enzyme in Gaucher's disease.

The accumulation of abnormal quantities of glu- cocerebroside in the reticuloendothelial cells of patients with Gaucher's disease is well documented (2-7). Previous studies in this laboratory indi- cated no abnormality in cerebroside formation in spleen tissue obtained from patients with Gauch- er's disease (8). These observations suggested that the biochemical lesion in these patients might be on the pathway of cerebroside catabolism. To pursue such investigations, we chemically synthe- sized glucocerebroside-14C labeled in carbon atom 1 of the D-glucose portion of the cerebroside mole- cule (9). With this material, it was possible to demonstrate and partially purify an enzyme in human spleen tissue that catalyzes the hydrolysis of the glycosidic bond of the cerebroside molecule. The products of the reaction catalyzed by the most highly purified enzyme preparation were shown to be glucose and ceramide (N-acylsphingosine) (9). When this information became available, stud- ies were undertaken to determine the level of the glucocerebroside-cleaving enzyme in human spleen tissue obtained from patients with various condi- tions. The present report describes the results obtained in these experiments and presents evi- dence of a marked attenuation of glucocerebrosidecleaving activity in the spleen of patients with Gaucher's disease.