A Rare Case of Adult-onset Niemann-Pick Disease Type C with PEX6 Mutation: Novel Genetic Insights

Background: Niemann-Pick disease type C (NPC) is a rare autosomal recessive neurodegenerative disorder. Adult-onset presentations are particularly uncommon and often misdiagnosed. Here, we report a rare case of NPC type C associated with a novel mutation in NPC1 and an additional mutation in the PEX6 gene, which has not been previously documented. Methods: A detailed clinical evaluation, laboratory investigations, imaging studies, and whole-exome sequencing were conducted. Results: A 29-year-old male presented with neuropsychiatric symptoms and splenomegaly. Genetic testing identified two significant mutations: c.3591+3G>T in NPC1 and c.2256del in PEX6. Clinical features were consistent with NPC type C1; however, no phenotypic expression of PEX6 mutation was observed, its potential modifying effects cannot be excluded. Conclusions: This case highlights the diagnostic challenges and genetic complexity of NPC, emphasizing the importance of genetic testing in rare diseases. Further studies are required to explore the clinical significance of co-occurring mutations. A lack of access to specific NPC therapies and long-term follow-up data remains a challenge in such rare cases.