NP-C is a lysosomal lipid storage disorder caused by mutations in NPC1 or NPC2 genes. NP-C can present with a range of visceral, neurological and psychiatric symptoms that vary with age. A suspicion index (SI) tool was developed to assist clinicians achieve early diagnosis. The tool accurately predicts NP-C in patients >4 years of age but performs poorly in paediatric (≤4 years) patients. The present study aimed to utilise the characteristic symptomatology of NP-C in paediatric patients to develop a novel tool to assist paediatricians to identify patients for NP-C testing.
Paediatric patients were classified according to diagnosis: NP-C suspected and confirmed (n = 106); NP-C suspected but negative (n = 31); control (no suspicion of NP-C; n = 63). Symptomatology data were collected retrospectively by questionnaire and summarised descriptively. The relationships between individual symptoms and likelihood of confirmed diagnosis of NP-C were defined by statistical modelling. The final tool was developed iteratively using combinations of symptoms until optimal discriminatory power was achieved.
The characteristic symptomatology of paediatric NP-C patients was identified; visceral symptoms were more prominent compared with older patients. The new tool discriminates well between NP-C confirmed, NP-C negative and control subjects. Statistical analysis demonstrates superior sensitivity and specificity of the paediatric tool compared to the original tool. The newly developed paediatric NP-C SI tool will help paediatricians to identify more paediatric patients with a high suspicion of NP-C, leading to more referrals for specialist testing thus improving early diagnosis and management of NPC-disease in paediatric patients.
Supported by Actelion Pharmaceuticals Ltd.