Niemann-Pick disease

Results of the investigation carried out during this decade brought unambigous evidence of biochemical heterogeneity inside the complex of Niemann-Pick disease according to which two entirely different metabolic disorders can be recognized. 1. Niemann-Pick sphingomyelinosis, a clear-cut enzymopathy, the pivotal lesion of which is the deficiency of lysosomal spingomyelinase leading to widespread lysosomal deposition of sphingomyelin liquid crystals. Two main allelic variants are known. The first one, neuronopathic (former type A) known as infantile with rapid course, may also manifest considerably prolonged course or an atypical course with predominantly visceral symptomatology. Patients with the second, visceral, variant (former type B), display mainly slow clinical course and often reach adulthood. With rare exceptions the neuronopathic variant can be biochemically recognized from the visceral one by much lower values of the in vivo sphingomyelin degradation test in the former. 2. The rest of the complex comprising types C-D differs substantially from the sphingomyelinase deficiency group by the remarkable heterogeneity in the lysosomal stored lipid pattern given by differences among the affected cell populations. Sphingomyelin storage could be proved histochemically solely in the histiocytic population together with cholesterol, neutral glycosphingolipids and lysobisphosphatidic acid, whereas the brain neurons displayed only neutral glycosphingolipid storage. There is an increasing evidence of the crucial biochemical lesion in this group being an altered intracellular traffic of exogenously derived cholesterol caused probably by its deficient translocation from lysosomes to other intracellular membrane sites. This leads to decreased cholesterol esterification rate which is the basis of the newly developed diagnostic test. Inconstant depression of sphingomyelinase activity is considered to be a secondary phenomenon. The so-called lactosylceramidosis is a rare variant pertinent to this group. The biochemical nature of type E still awaits clarification. Both groups of Niemann-Pick disease display clinical and especially histochemical features which allows to establish diagnosis in a highly efficient way already at the clinicopathological level.