Systematic review of psychiatric signs in Niemann-Pick disease type C.

We conducted the first systematic literature review and analysis of psychiatric manifestations in Niemann-Pick disease type C (NPC) to describe: (1) time of occurrence of psychiatric manifestations relative to other disease manifestations; and (2) frequent combinations of psychiatric, neurological and visceral disease manifestations. A systematic literature search was conducted to identify, collate and analyze published data from patients with NPC associated with psychiatric symptoms, published between January 1967 and November 2015. Of 152 identified publications 40 were included after screening that contained useable data from 58 NPC patients (mean [SD] age at diagnosis of NPC 27.8 [15.1] years). Among patients with available data, cognitive, memory and instrumental impairments were most frequent (90% of patients), followed by psychosis (62%), altered behavior (52%) and mood disorders (38%). Psychiatric manifestations were reported before or at neurological disease onset in 41 (76%) patients; organic signs (e.g., hepatosplenomegaly, hearing problems) were reported before psychiatric manifestations in 12 (22%). Substantial delays to diagnosis were observed (5-6 years between psychiatric presentation and NPC diagnosis). NPC should be considered as a possible cause of psychiatric manifestations in patients with an atypical disease course, acute-onset psychosis, treatment failure, and/or certain combinations of psychiatric/neurological/visceral symptoms.