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.