Diagnosis and Outcomes of Late-Onset Wilson's Disease: A National Registry-Based Study.

BACKGROUND: Wilson's disease (WD) is usually diagnosed in children and young adults; limited data exist on late-onset forms. OBJECTIVE: The aim was to characterize the clinical and paraclinical presentations, therapeutic management, and outcomes in patients with late-onset WD. METHODS: Patients diagnosed with WD after age 40 years were identified from the French Wilson's Disease Registry (FWDR). Clinical, laboratory, and imaging findings and treatment were reported at diagnosis and last follow-up. RESULTS: Forty-five patients were identified (median age: 49, range: 40-64) and placed in three groups according to their clinical presentation: neurological (n = 20, median diagnostic delay: 20 months), hepatic (n = 13, diagnostic delay: 12 months), and family screening (n = 12), all confirmed genetically. Six neurological patients had an atypical presentation (1 torticollis, 2 writer's cramps, 2 functional movement disorders, and 1 isolated dysarthria), without T2/fluid-attenuated inversion recovery brain magnetic resonance imaging (MRI) hyperintensities; 5 of 6 had no Kayser-Fleischer ring (KFR); 5 of 6 had liver involvement. In the neurological group, 84% of patients improved clinically, and 1 developed copper deficiency. In the hepatic group, 77% had cirrhosis; 6 patients required liver transplantation. In the screened group, 43% had mild liver involvement; 3 were not treated and remained stable; 24-h urinary copper excretion was normal in 33% of patients at diagnosis. CONCLUSIONS: In the FWDR, late-onset forms of WD affect 8% of patients, mostly with neurological presentations. Thirty percent of the neurological forms were atypical (isolated long-lasting symptoms, inconspicuous brain MRI, no KFR). With personalized treatment, prognosis was good. This study emphasized that WD should be suspected at any age and even in cases of atypical presentation. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Maintenance therapy simplification using a single daily dose: A preliminary real-life feasibility study in patients with Wilson disease.

BACKGROUND: Single daily dose (SDD) is a good way to improve adherence by simplifying treatment. Efficacy data concerning patients with Wilson disease (WD) taking an SDD are lacking. AIM: To report the effectiveness of the use of SDD for the treatment of WD. METHODS: This retrospective study included WD patients followed in the French National Network who received an SDD in maintenance phase. The treatment failure was defined as a composite criterion with the occurrence of at least one of the following criterion: death, transplantation, increase of transaminases >2xULN, hepatic decompensation, neurological aggravation, severe side effects related to treatment, and/or discontinuation of treatment. RESULTS: A total of 26 patients received an SDD (D-penicillamine=13, trientine=8, zinc=5) after a median interval of 152 months after diagnosis. After one year, two patients had treatment failure: transaminitis in one, continuation of neurological deterioration in the other related to a poor compliance. After a median duration of 41 months on SDD, 3 other patients had treatment failure (transaminitis=2, treatment discontinuation=1). There was no death, no liver transplantation, no hepatic decompensation, and no severe side effects related to treatment during the follow-up. Moreover, transaminases and serum exchangeable copper were not significantly different 1 year post-switch and at last follow-up compared to baseline. CONCLUSIONS: Maintenance therapy simplification through the use of an SDD could be considered in some WD patients. In this pilot study, SDD was effective in 21/26 patients (81%) without any concern regarding safety.