Sphingosylphosphorylcholine in Niemann-Pick disease brain: accumulation in type A but not in type B.

A study of brain lipids in patients with the sphingomyelinase-deficient types of Niemann-Pick disease demonstrated that abnormal accumulation of sphingomyelin occurs only in the brain of neuronopathic type A patients but not in the non-neuronopathic type B. Additional lipid abnormalities were present in the type A brain. In contrast, the brain lipid profile was normal in type B patients. Since lysosphingolipids have been implicated in the biochemical pathogenesis of other genetic lysosomal sphingolipidoses, the occurrence of sphingosylphosphorylcholine (lysosphingomyelin) was specifically investigated in brain and extraneural tissues, using an HPLC method with fluorescent detection of orthophtalaldehyde derivatives. Levels close to or below the limit of detection (10 pmol/mg tissue protein) were observed in normal and pathological controls. A striking accumulation was observed in brain of two Niemann-Pick type A patients (830 and 430 pmol/mg protein in 27-and 16-month-old children with severe and milder neurological course, respectively), which was not present at the fetal stage of the disease. No significant increase was found in brain tissue from a 3.5 year-old type B patient. In liver and spleen, abnormally high sphingosylphosphorylcholine levels were observed in both types of the disease, with indication of a progressive increase during development. This study establishes the integrity of brain tissue in Niemann-Pick disease type B and suggests that the lysocompound sphingosylphosphorylcholine could play a role in the pathophysiology of brain dysfunction in the neuronopathic type A.