Niemann-Pick disease (variation in the sphingomyelinase deficient group)

Abstract

We report three families with five cases of sphingomyelinase (SMase) deficiency, early neurovisceral symptomatology, and a conspicuously protracted course (7–22 years) in contrast to the characteristic acute, rapidly lethal course in classical type A cases. Most of the visceral symptoms were hepatomegaly and splenomegaly, with numerous foam cells in the bone marrow, some of them containing ceroid (sea-blue histiocytes). Histochemical and chemical biopsy studies (liver, skin, bone marrow) revealed macrophage and epithelial sphingomyelinosis and profound SMase deficiency. The dominant neurological symptoms in three of the cases included extrapyramidal involvement, marked mental deficiency, and cherry red spots in the fundus oculi of all the 5 cases. There was, however, a striking variability in the clinical signs in three siblings. The first of them, a girl, died at 7 years from purely visceral involvement with massive affection of the lungs. Despite the absence of clinically detectable, neurological symptomatology there was discrete regional neuronal storage in the brain. Her two younger brothers are still alive. The elder one (22 years) has been reduced to complete neurological invalidism while his younger brother (18 years) has no demonstrable neurological changes, and enjoys normal social integration. Symptomatologically, he is difficult to distinguish from type B, especially from its rare variants with retinal involvement. The discussion is devoted to differences between types A and B of the SMase deficiency and to the neurological symptomatology apparently independent of the gene dose in the three siblings.