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Within Niemann-Pick diseases, type C has now been demonstrated to be a nosological entity totally distinct from types A and B, and is best characterized at present by unique abnormalities of intracellular translocation of exogenous cholesterol, which are briefly reviewed. Although the primary defect is still unknown in type C Niemann-Pick disease, this discovery has had immediate medical applications, by providing the first strategy for reliable prenatal detection of the disorder and easy diagnosis of patients. From our personal experience of 134 cases, diagnosis is best reached by the combined demonstration of a deficient induction of esterification and of an intravesicular cholesterol storage by cytochemistry after filipin staining. The prevalence of the various clinical forms observed is given, together with a brief report of 6 adult-onset cases. The spectrum of phenotypic heterogeneity in relation to abnormal LDL processing has been defined, resulting in the delineation of three biochemical groups, classical (86%), variant (7%) and intermediate (7%). Correlations between clinical and biochemical phenotypes have been studied. To get further insight into genetic heterogeneity, complementation studies were performed. Preliminary results have yet given no evidence of several complementation groups within type C Niemann-Pick disease. The recognition of the three biochemical phenotypes is however critical for diagnosis and genetic counselling.

We examined biochemically sphingomyelinase activity in the bovine and human ocular tissues, using trinitrophenylaminododecanoylsphingosylphosphorylcholine as substrate. The enzyme activity in the crude extracts of neuroretina, retinal pigment epithelial cells, and optic nerve of the bovine eyes was proportional to protein concentration. The activities in these tissues were little activated with Mg2+ at pH 5.1 but was activated with Mg2+ at pH 7.5. The enzyme activity at pH 5.1 was also detected in the iris and ciliary body, neuroretina, retinal pigment epithelium and choroid, and optic nerve of the human eyes. It was highest in the macula, compared with other areas of the human ocular fundus.