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Deficiency of phospholipase C acting on phosphatidylglycerol in Niernann-Pick disease

Neurology Program, Department of Medicine (Drs. Huterer and Wherrett) and the Division of Neurosciences, the Hospital for Sick Children (Drs. Poulos and Callahan), University of Toronto, Toronto, Ontario, Canada.

we examined the degradation of a labeled phosphatidylglycerol (PG) by fibroblasts from a normal control and a patient with Niemann-Pick (NP1 disease. The control homogenate had both phospholipase A and phospholipase C activities toward PG, but NP cells had only phospholipase A. The PG phospholipase C of control fibroblasts was solubilized by sonication and freezing and thawing, was most active at pH 5.0, and was inhibited by Ca²⁺, detergents, sphingomyelin, and 5' AMP. Assay of PG phospholipase C in fibroblast cultures from NP patients with sphingomyelinase deficiency (three designated type A and four type B) confirmed absence of activity, whereas cultures from NP patients without sphingomyelinase deficiency (three designated type C and one with neurovisceral lipidoses and vertical supranuclear ophthalmoplegia) had activities close to those of normal controls. These findings substantiate previous observations of low phosphodiesterase activities in NP disease and suggest that the enzymatic function affected by the NP genes includes specificity toward PG and sphingomyelin. Deficiency of PG phospholipase C may explain the accumulation of bis(monoacylg1ycero) phosphate in NP disease.

Address correspondence and reprint requests to Dr. Wherrett. Neurology Program, 6368 Medical Sciences Building, University of Toronto, Toronto, Ontario, Canada M5S 1A8.

Supported by grants from the Medical Research Council of Canada. Dr. Poulos was on study leave granted by the Department of Chemical Pathology, Adelaide Children's Hospital, Adelaide, South Australia.

Accepted for publication May 2l, 1982.