Clinical Characteristics, Genetic Features, and Long-Term Outcome of Wilson’s Disease in a Taiwanese Population: An 11-Year Follow-Up Study

Abstract

ObjectiveaaWilson’s disease (WD) is a rare genetic disorder of copper metabolism, and longitudinal follow-up studies are limited. We performed a retrospective analysis to determine the clinical characteristics and long-term outcomes in a large WD cohort.MethodsaaMedical records of WD patients diagnosed from 2006–2021 at National Taiwan University Hospital were retrospectively evaluated for clinical presentations, neuroimages, genetic information, and follow-up outcomes.ResultsaaThe present study enrolled 123 WD patients (mean follow-up: 11.12 ± 7.41 years), including 74 patients (60.2%) with hepatic features and 49 patients (39.8%) with predominantly neuropsychiatric symptoms. Compared to the hepatic group, the neuropsychiatric group exhibited more Kayser-Fleischer rings (77.6% vs. 41.9%, <i>p</i> < 0.01), lower serum ceruloplasmin levels (4.9 ± 3.9 vs. 6.3 ± 3.9 mg/dL, <i>p</i> < 0.01), smaller total brain and subcortical gray matter volumes (<i>p</i> < 0.0001), and worse functional outcomes during follow-up (<i>p</i> = 0.0003). Among patients with available DNA samples (<i>n</i> = 59), the most common mutations were p.R778L (allelic frequency of 22.03%) followed by p.P992L (11.86%) and p.T935M (9.32%). Patients with at least one allele of p.R778L had a younger onset age (<i>p</i> = 0.04), lower ceruloplasmin levels (<i>p</i> < 0.01), lower serum copper levels (<i>p</i> = 0.03), higher percentage of the hepatic form (<i>p</i> = 0.03), and a better functional outcome during follow-up (<i>p</i> = 0.0012) compared to patients with other genetic variations.ConclusionaaThe distinct clinical characteristics and long-term outcomes of patients in our cohort support the ethnic differences regarding the mutational spectrum and clinical presentations in WD.