Two siblings of consanguinous parents were noted to have a neurologic syndrome irarked by developmental delay, regression of psychomotor performance, marked spasticity and progressive central nervous system degeneration. Markedly delayed nerve conduction times and a sural nerve biopsy which demonstrated changes typical of metachromatic leukodystrophy (MLD) were evident. Impairment of sulfated alycolipid metabolism was documented by analysis of glycospingo- lipid in urinary sediment. In spite of these findings, activities of aryl- sulfatase A and cerebroside sulfatidase in white blood cells and cultured skin fibroblasts were near normal. However, when intact growing fibroblasts were loaded with35SO4-sulfatide a clear defect in sulfatide cleavage, comparable to that seen in MLD patients, was observed, Thus, these patients represent a new form of sulfatide storage disease - MLD characterized by intact enzyme activity in cell homogenates but defective sulfolipid metabolism in vivo and in intact fibroblasts. Speculation Since cell homogenates from these patients can cleave sulfatide in the presence of detergents while the patients themselves and their intact cells cannot, some explanation other than decreased activity of the relevant lysosomal enzyme must be invoked to explain this storage disease. The two most plausible hypotheses are that either these patients have a defect which prevents enzyme and substrate interaction in the proper subcellular location, or that these patients are missing the putative glycoprotein "activating factor" necessary for sulfolipid hydrolysis in vivo.
|Number of pages||3|
|State||Published - Oct 1979|