P16. Neurologic-psychiatric disease patterns in Niemann-Pick type C disease: A cohort study on 14 Suisse patients

Abstract

Niemann-Pick disease type C (NP-C) is a rare autosomal recessive disorder of lysosomal cholesterol transport. The diagnosis of NP-C disease still poses a considerable challenge to clinicians, hampered by the lack of specific biomarkers and a remarkable clinical heterogeneity. The objective of this study was to critically analyze the onset and time course of symptoms, and the clinical diagnostic work-up of NP-C disease in a national Swiss cohort. Clinical, biochemical and genetic data were collected from 14 patients diagnosed with NP-C between 1994 and 2013. Diagnostic delays were calculated for neurological, psychiatric and visceral symptoms associated with NP-C disease. We further retrospectively evaluated prevalence rates of clinical symptoms during the observation period ending in September 2013. In our cohort, neurological symptoms showed a median diagnostic delay of 5 years. Among these, vertical supranuclear gaze palsy, dysphagia and seizures had the shortest median diagnostic delays of 2 years and 3 years for the latter. Neurological symptoms such as ataxia, dysarthria, spasticity and cataplexy displayed a median diagnostic delay of 4–5 years, similar to psychiatric symptoms such as cognitive decline.Visceral symptoms, in particular hepatosplenomegaly, were associated with the longest median diagnostic delay of 13 years. Highest prevalence rates were noted for ataxia, dysarthria, VSGP and cognitive decline. All of these symptoms showed an early onset within the first and second decade, respectively. A neurologic-psychiatric disease pattern may represent the most characteristic clinical manifestation of NP-C and occurs early in the disease course. Patients with neurological & psychiatric disorders of unclear etiology should be investigated for accompanying organomegaly.