Early Diagnosis of Nieman–Pick Disease Type C and Rapid Response of Gelastic Cataplexy to Treatment With N-Acetyl-L-Leucine: A Case Report

BACKGROUND Niemann-Pick disease type C (NPC) is a rare, progressive neurodegenerative lysosomal storage disorder often diagnosed in childhood after the onset of neurological symptoms. Gelastic cataplexy - the sudden loss of muscle tone associated with laughter but remaining consciousness - is quite specific for NPC. This report describes the case of a 4-year-old boy with NPC presenting with gelastic cataplexy who responded to treatment with N-acetyl-L-leucine (NALL). CASE REPORT We present the case of a patient who first presented in the genetics clinic due to hepatosplenomegaly, dysmorphic features, and milestone delay at 2 years old. He had a history of cholestatic jaundice and hepatosplenomegaly at 2 months old. Granulomatous hepatitis of unknown origin was diagnosed by liver biopsy, and then the cholestatic jaundice resolved. The diagnosis of NPC was made, confirmed by compound heterozygous missense likely pathogenic in NPC1 (NM_000271.5): one known; c.2072C>T (p.Pro691Leu), and one novel; c.2805A>G (p.Ile935Met) at the age of 3 years. He then developed gelastic cataplexy at the age of 4 years, and a clinical improvement was observed within the first month after receiving NALL, including a significant decrease in cataplexy episodes, improved motor function, and reduced splenomegaly. CONCLUSIONS This case highlights the critical role of early genomic diagnosis in NPC, enabling prompt management of worsening neurological symptoms and potentially responding to treatment with NALL.