The possibility of patients with adult-onset Niemann-Pick disease type C in cases diagnosed with schizophrenia: Analysis of NPC novel biomarkers.

BACKGROUND: When patients with schizophrenia on antipsychotic medication present neurological symptoms, it is often considered to be side effects of antipsychotics. In contrast, Niemann-Pick disease type C (NPC) has a wide variety of symptoms, and the diagnosis of adult-onset NPC is difficult. In this study, we measured novel biomarkers of NPC and examined the possibility of NPC in patients diagnosed with schizophrenia.

METHODS: Five patients with schizophrenia and neurological symptoms were evaluated using the NPC Suspicion Index, and urinary bile acid and blood oxysterol levels were measured by LC-MS/MS and Q-TOF LC/MS. Lysosphingomyelin (SPC) and Lyso-SM-509(PPCS), reported as novel biomarkers for NPC, were measured in the plasma of 163 patients with schizophrenia and 111 healthy controls using LC-MS/MS. NPC1 and NPC2 gene analyses were performed on 124 patients using the next-generation sequencer. In one patient, Filipin staining was performed using skin fibroblasts.

RESULTS: Among the five patients, one patient had an abnormal urinary bile acid level. Levels of SPC were significantly higher in patients than in healthy controls. Genetic analysis revealed no genetic mutations associated with the etiology. The patient who underwent Filipin staining had cholesterol-stained pale and was determined to be a variant type. However, it would be more accurate to state that no patients were identified as NPC based on these biomarkers.

CONCLUSION: Among the patients with schizophrenia, there were no cases that were definitively diagnosed as NPC, but some patients had features of NPC. It is important to evaluate mental and neurological symptoms in light of this possibility.