High diagnostic value of plasma Niemann-Pick type C biomarkers in adults with selected neurological and/or psychiatric disorders

The objective of our study was to evaluate practical utility and feasibility of large-scale PSB screening for NP-C in sel ected adult patients. Patients were prospectively enrolled if they showed, starting from 12 years of age, at least one of the three initial neuro-psychiatric manifestations described in NP-C: (1) gait disorder (cerebellar and/or dystonic); (2) cognitive decline with frontal lobe syndrome; (3) atypi cal psychosis. PSBs were measured in plasma of all patients and, if positive (LSM-509 and/or C-triol + 7-KC elevated), sequencing ofNPC1 andNPC2 genes was performed. A total of 251 patients [136 males, 115 females; median age 42.1 (range 12.2 –85.6) years] were screened. Six patients had positive PSBs. Two were confirmed to have NP-C (0.8% diagnostic yield, both with all three PSBs highly increased, especially LSM-509). False-positive rate was 1.2%, which was identical if only considering LSM-509. By contrast, false-positive rates were 8.1% and 5.7% for 7-KC and C-triol, respectively. We showed that selecting patients with neurologic and/or psychiatric symptoms consistent with NP-C for large-scale PSB screening is a simple and valid strategy to identify new adult NP-C patients, and would probably lead to earlier diagnosis and tre atment administration if widely applied.
Source: Journal of Neurology - Category: Neurology Source Type: research