Chemical Studies in Gargoylism * J 0 RGEN CLAUSEN , HOLGER V . DYGGVE , JOHANNES C . MELCHIOR , and HANS OLAV

Recent studies of the chemical structure of glycolipids (Klenk and Gielen, 1961, 1963; Svennerholm and Raal, 1961; Kuhn, 1961; Wolfe and Lowden, 1964) have contributed to our knowledge of the metabolism of different glycolipids. Thus, a low concentration of 3-glucosidase in human brain and other organs will give rise to a blocked degradation of gangliosides, with accumulation of glucocerebrosides, the disease associated with this enzymatic defect having previously been named Gaucher's disease (Gaucher, 1882; Philippart and Menkes, 1964; Brady, Kanfer, and Shapiro, 1965a, b; Svennerholm, 1966). Again, the gluco-cerebrosides in brain may be transformed by means of specific enzymes to galacto-cerebrosides. This ceramide, as well as galacto-gluco-ceramide, may be sulphated by means of active sulphate (Svennerholm, 1966), to give rise to sulphatides which in their turn are degraded by the action of sulphatases (Mehl and Jatzkewitz, 1963, 1964), so that absence of the enzyme sulphatase, as occurs in metachromatic leucodystrophy, results in accumulation of the sulphatides (Jatzkewitz, 1960; Sourander and Svennerholm, 1962; Hagberg, Souranderand Svennerholm, 1962; Austin, McAfee, Armstrong, O'Rourke, Shearer, and Bachhawat, 1964). Finally, the initial splitting of N-acetyl-neuraminic acid (NANA) may be impaired, as is the case in Tay-Sachs' disease (Klenk, Liedtke, and Gielen, 1963), when mainly mono-sialo-gangliosides accumulate. Accumulation of carbohydrate derivatives occurs not only in the lipidoses but also in the mucopolysaccharidoses (Melchior, Clausen, and Dyggve, 1965). Thus, in Hurler's syndrome (gargoylism) there are accumulations of chondroitin sulphate B and heparitin sulphate (Brante, 1952; Bishton,