Studies concerning the pathogenesis of Gaucher's disease.

By BERTHA OTTENSTEIN, Ph.D., GERHARD SCHMIDT, M.D., AND S. J. THANNHAUSER, M.D. I N 1882. Charles Ernst Gaucher’ described as “epithelioma primitif de Ia rate” the disease which now bears his name. In his case he found the splenic pulp entirely replaced by large cells and attributed this condition to a primary tumorous growth, epithelioma of the spleen. Collier2 (1895) in England, and Picou and Ramond3 in France (1896) also regarded the condition as neoplastic. Bovaird4 (I9oo), reporting the first case in this country, called attention to the simultaneous appearance of these large cells in the liver as well as in the spleen and lymph nodes. He had commented on the familial character of the disease. In contrast to the current view that the disease was of tumorous nature, he believed that an unknown toxin caused hyperplasia of spleen, liver, and lymph nodes. Brill, Mandlebaum and Libman5 (19o5) were the first to point out that the cells which characterized the disease were found, not only in the liver, spleen and lymph nodes, but appeared simultaneously in different parts of the skeleton. These authors suggested (1913) the name, ‘Gaucher’s disease,” to avoid the misleading term “primary idiopathic splenomegaly.” Schlagenhaufer6 (19o6) considered that the condition was a systemic disease of the lymphhemapoietic tissue. H. Lieb7’ 8 (192.4, 192.5), in association with Epstein and Lorenz,9 isolated the substance which characterized the Gaucher cells and identified this substance as a cerebroside, namely kerasin. It was believed that kerasin, a galactosidocerebroside, was a constituent only of brain tissue and not of visceral organs. L. Pick’#{176}assumed that kerasin originated as a result of a general disturbance of intermediary lipid metabolism, accumulated in the blood, and was secondarily deposited and stored in the reticulum cells of the involved organs. He characterized Gaucher’s disease “not as a reticulo-endothelial, reticular cell or histiocytomatotic disease, but as a histiocytic disease comparable to histiocytic storage as observed in vital staining or cholesterol feeding of animals with, however, elective participation of certain histiocytic forms.” In contrast to the conception of L. Pick,’#{176}S. J. Thannhauser and co-workers” demonstrated that normal serum or serum of patients with Gaucher’s disease did not contain measurable amounts of cerebrosides. This observation was subsequently confirmed by Dvoracek and Pest,’2 and Bruckner’3: Since cerebrosides are not present in the serum of Gaucher’s disease, Thannhauser’4 concluded that cerebrosides do not originate as a result of a general disturbance of the intermediary lipid metabolism but are synthesized and stored in the cells where they are found; i.e., in the Gaucher cells. This explanation of the pathologic formation of cerebrosides places the metabolic disorder within the reticulum cells and histiocytes.