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

Abstract

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.

Wilson’s Disease: A Prevalence Study in a Portuguese Population

“…In this study, WD presented mostly as hepatic symptoms (54.8%, n = 46) and less frequently neuropsychiatric (10.7%, n = 9), also consistent with previous studies where hepatic manifestations are reported in 45% [ 7 , 16 ]. As already described in the latest European Association for the Study of the Liver (EASL) guidelines on WD, hepatic manifestations are highly variable, ranging from asymptomatic to overt cirrhosis and fulminant hepatitis [ 16 ]. A liver transplant was accomplished in 23.9% (n = 21), mostly in the context of fulminant hepatitis.…”

“…A liver transplant was accomplished in 23.9% (n = 21), mostly in the context of fulminant hepatitis. The age of presentation for predominantly neurological patients is described to be between 20 and 30 years of age and mainly hepatic manifestations often present between 10 and 13 years of age [ 16 - 18 ]. Neurological patients are, therefore, diagnosed at an older age, about 10 years later in comparison with that described in other studies and an average of five years in our sample [ 16 ].…”

Treating the Neurologic Manifestations of Wilson’s Disease With Liver Transplantation

“…The French Wilson's Disease Registry reported 8% of their cohort (45) patient were diagnosed after age 40 years (median age 49). 6 Many patients with these later diagnoses had predominantly neurologic presentations with potentially isolated long-lasting symptoms (including writer's cramp, cervical dystonia, and functional neurologic disorders-tremor and myoclonus). There was a notable absence of KF rings and MRIs were unremarkable.…”

Challenges with neuropsychiatric Wilson's disease

“…It is worth noting that a neuropsychiatric presentation in Wilson's disease has previously been associated with diagnostic delays and late‐onset disease. 2 , 3 However, even in the late‐onset cases with neurological presentation, the majority of patients improve clinically with treatment. 2 While it is standard practice to consider Wilson's disease in the diagnostic evaluation of acute and chronic liver diseases, the same level of suspicion may not always extend to patients presenting with diverse neuropsychiatric symptoms without obvious liver abnormalities.…”

“… 2 , 3 However, even in the late‐onset cases with neurological presentation, the majority of patients improve clinically with treatment. 2 While it is standard practice to consider Wilson's disease in the diagnostic evaluation of acute and chronic liver diseases, the same level of suspicion may not always extend to patients presenting with diverse neuropsychiatric symptoms without obvious liver abnormalities. This underscores the need for clear guidelines on when to suspect Wilson's disease in the diagnostic evaluation of especially adult patients presenting with neuropsychiatric symptoms.…”