Sea-blue histiocytosis in a family with Niemann-Pick disease. A clinical, morphological and biochemical study.

Four siblings of a large Brazilian kindred are shown to have a variant of Niemann-Pick disease masquerading as the sea-blue histiocyte syndrome. They show a very similar clinical and laboratory picture: massive hepatosplenomegaly, low height for age, diffuse interstitial pulmonary infiltration, high levels of serum acid phosphatase and sea-blue histiocytes in the bone marrow. The neurological examination, as well as the retinae and maculae are normal. The high-density lipoprotein serum cholesterolemia ranged from 8.6 to 13.9 mg/dl, much lower than the 5th centile of normal distribution. The AI apolipoprotein concentrations in two siblings (0.29 and 0.44 g/l) were also below the minimal reference level of 0.90 g/l. The histochemical reactions demonstrated that sphingomyelin and ceroid are the accumulating substances in the marrow histiocytes. Electron microscopically, the cytoplasmatic granules of the histiocytes are phagolysosomes which contain scarce amorphous material, loose arranged lamellae, or dense well-organized structures with a fingerprint or fine network pattern. The sphingomyelinase activity in leucocyte extracts ranged from 4.9 to 8.6% and in cultured fibroblast extracts from 7.7 to 10% of simultaneous controls. The activity of other lysosomal enzymes was normal. Accordingly, this variant of Niemann-Pick disease should be classified as chronic nonneuronopathic sphingomyelinase-deficient type. The present data suggest that this variant is inherited as an autosomal recessive character. Our findings support the view that the sea-blue histiocyte syndrome is not an independent entity.