Niemann-Pick disease type C (NPC) is a lipid storage disease presenting in infants, children or adults. NPC is inherited in an autosomal recessive manner and has a frequency of about 1 in 150,000 persons. The classic presentation occurs in middle to late childhood with the insidious onset of ataxia, vertical supranuclear gaze palsy, dementia, dystonia and seizures. The seizures are partial or generalized, or both. The epilepsy is often refractory to medical therapy, but improves if survival is prolonged, presumably reflecting neuronal loss. About 20% of affected children have cataplexy induced by laughing. Dysarthria and dysphagia eventually become disabling, making oral feeding impossible. Adults are more likely to present with dementia or psychiatric symptoms. The diagnosis of NPC is confirmed by bone marrow biopsy which shows lipid-laden histiocytes, the biochemical demonstration of impaired cholesterol esterification and positive filipin staining in cultured fibroblasts. The diagnosis is often delayed substantially because 'routine' screening tests for metabolic disease, such as urine screens and lysosomal enzyme panels, are negative. In about 90% of cases NPC is caused by an identifiable mutation in the NPC1 gene (and a handful of cases have been described with NPC2 gene mutations). Molecular genetic testing is available.
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