Niemann-Pick disease type C (NPC) is a cholesterol storage disease caused by defective cellular cholesterol transportation. The onset and progression of NPC are variable, and autopsy findings have mainly been reported for the adult and juvenile forms of this disease. Here we report the clinical and pathological findings from a 9-year-old female patient with the late infantile form of NPC due to NPC1 gene mutation. She had notable splenomegaly at 4 months of age. She lost the ability to speak at 18 months of age. She learned to walk, but often fell and could no longer walk after 30 months. At 3 years of age, she was diagnosed with NPC. Sequence analysis of the NPC1 gene revealed compound heterozygous mutation of T2108C (F703S) and C2348G (S813X) (both novel). Thereafter, the patient suffered repeated respiratory infections and died of respiratory failure at 9 years of age. Pathological findings included cerebral atrophy (particularly of white matter), severe demyelination, and the loss of neurons from the cerebrum and from the nuclei of the brain stem. Remnant neuronal cells and microglia in the cerebrum, cerebellum, and brain stem had become swollen and foamy. Neurons of the hippocampal CA1 and Purkinje cells were relatively spared, and senile plaques and axonal spheroids were not present. Foamy cells were also observed in other organs, especially the spleen and bone marrow. The F703S mutation in this patient was localized in a sterol-sensing domain (SSD). Severe neurological phenotypes have been previously reported in patients with missense mutations in an SSD. It is considered that the combination of a nonsense mutation and missense mutation in an SSD was responsible for the severe neurological phenotype of our present patient. While pathological findings of adult/juvenile forms of NPC have included swollen neurons and glia, neuronal cell loss, and NFTs, demyelination may be a predominant finding in the infantile form of NPC.

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