Long-term misdiagnosis of Niemann-Pick disease type C as Wilson disease: A case report

Niemann-Pick disease type C (NPC) is a rare autosomal recessive lysosomal lipid storage disorder caused by pathogenic variants in NPC1 or NPC2. Adult-onset NPC may manifest with progressive ataxia, dysarthria, cognitive impairment, psychiatric symptoms, and splenomegaly, features that may overlap with Wilson disease (WD). Abnormal copper metabolism in NPC can further complicate the differential diagnosis.

A 39-year-old man was admitted with a more than 15-year history of slowly progressive dysarthria and gait instability, accompanied by intermittent choking when drinking and mild recent memory impairment. He had previously been diagnosed with WD because of splenomegaly, low serum ceruloplasmin, and increased 24-hour urinary copper excretion, and had received intermittent copper-chelating therapy. His 42-year-old sister had similar neurological symptoms and had also been diagnosed with WD.

On readmission, the patient had leukopenia, splenomegaly, low serum ceruloplasmin, and elevated 24-hour urinary copper excretion. His Leipzig score was 4, meeting the diagnostic threshold for WD. However, Kayser-Fleischer rings were absent, brain magnetic resonance imaging showed no typical abnormalities suggestive of neurological WD, and the disease course was unusually indolent despite long-term irregular anti-copper treatment. Genetic testing of the proband and his affected sister identified compound heterozygous pathogenic variants in NPC1, c.2932C > T (p.Arg978Cys) and c.2974G > T (p.Gly992Trp), confirming the diagnosis of NPC.

Copper-chelating therapy was discontinued after the diagnosis was revised. The patient was started on miglustat, initially at 0.2 g once daily, which was gradually increased to 0.2 g 3 times daily.

After 3 months of follow-up, the patient's dysphagia improved, whereas gait instability persisted.

Adult-onset NPC can mimic WD clinically and biochemically. Because copper metabolism abnormalities are not pathognomonic for WD, they may yield misleadingly high Leipzig scores. NPC should be prioritized in patients with progressive neurological decline and splenomegaly who lack classic WD hallmarks, such as Kayser-Fleischer rings or characteristic neuroimaging findings. Early genetic testing is essential to ensure diagnostic accuracy and avoid inappropriate long-term copper-chelating therapy.