NERVE BIOPSY FINDINGS IN NIEMANN-PICK TYPE-II (NPC)

The severe infantile form of Niemann-Pick disease type II was diagnose d in a 4-year-old girl and confirmed by demonstrating in cultured skin fibroblasts a deficiency of low-density lipoprotein-stimulated choles terol ester synthesis of < 5 % of normal. Electrodiagnostic studies re vealed changes of a predominantly demyelinating motor and sensory poly neuropathy. Light microscope and ultrastructural examination of a pero neal nerve biopsy showed unique changes. Compacted myelin sheaths were disproportionately thin with marked globular irregularities in single teased nerve fibres and evidence of chronic demyelination. The majori ty of axons were preserved but axonal spheroids and cytoskeletal abnor malities akin to neuroaxonal dystrophy were noted. Membrane-bound mult i-lobulated lysosomal inclusions of floccular and electron-dense mater ial were present in Schwann cells (SC), endoneurial fibroblasts, macro phages, pericytes and endothelial cells. SC of myelinated fibres were stuffed with whorls of concentric osmiophilic membranous profiles and electron-lucent material. The findings are diagnostic and differ from those of classical Niemann-Pick disease.