Abnormal copper metabolism in Niemann–Pick disease type C mimicking Wilson's disease

Background Niemann–Pick disease type C is a rare lysosomal storage disease in infants, adolescents and adults. Aim We investigated a family with two siblings who have adult‐onset Niemann–Pick disease type C presenting with abnormal copper metabolism mimicking Wilson's disease. Methods Case 1 was a 26‐years‐old Japanese man without consanguinity, and was referred to the hospital outpatient clinic for recent gait disturbance and intellectual deterioration developing since the age of 20 years. He was tentatively diagnosed as a heterozygous carrier of Wilson's disease, because his brother (case 2) had been diagnosed with Wilson's disease. He presented with dementia, dysphagia, dystonia, ataxia and downward gaze palsy. Laboratory study showed mild liver dysfunction and moderate splenomegaly. Magnetic resonance images showed a thin corpus callosum and narrowed deep white matter. Case 2 35 years‐of‐age, and had developed psychiatric and motor symptoms since 20 years‐of‐age. He had been treated for Wilson's disease for 11 years due to a copper deposit in his liver and abnormal copper metabolism. Symptoms had exacerbated gradually despite chelation therapy and tube feeding with gastrostomy for a year. Molecular diagnostics for Niemann–Pick disease type C were carried out. Results Filipin staining in cultured skin fibroblasts of case 1 was partially positive, and gene analysis showed that both siblings had compound heterozygosity for p.G992R in exon 20 and IVS 6‐3 C>G of NPC 1 . Administration of miglustat for 3 months partially ameliorated their intellectual and motor dysfunction. Conclusion The differential diagnosis between Niemann–Pick disease type C and Wilson's disease is important for specific treatment.