Wilson disease

Abstract

Purpose of review The aim of this article is to review recent developments in the areas of the disease features and treatment of Wilson disease, and survey disorders that share its pathophysiology or clinical symptoms. Recent findings Knowledge of the clinical spectrum of Wilson disease has expanded with recognition of patients who present in atypical age groups – patients with very early onset (<5 years) and those in whom symptoms present in mid-to-late adulthood. A disease phenotype with dominant psychiatric features and increased risk of cardiac problems and various sleep disorders have been identified. In addition to a better understanding of the phenotype of Wilson disease itself, features of some related disorders (‘Wilson disease-mimics’) have been described leading to a better understanding of copper homeostasis in humans. These disorders include diseases of copper disposition, such as mental retardation, enteropathy, deafness, neuropathy, ichthyosis, keratoderma syndrome, Niemann–Pick type C, and certain congenital disorders of glycosylation, as well as analogous disorders of iron and manganese metabolism. Outcomes for existing treatments, including in certain patient subpopulations of interest, are better known. Novel treatment strategies being studied include testing of bis-choline tetrathiomolybdate in phase 2 clinical trial as well as various preclinical explorations of new copper chelators and ways to restore ATP7B function or repair the causative gene. Summary Recent studies have expanded the phenotype of Wilson disease, identified rare inherited metal-related disorders that resemble Wilson disease, and studied long-term outcomes of existing treatments. These developments can be expected to have an immediate as well as a long-term impact on the clinical management of the disease, and point to promising avenues for future research.

Effects of High-Frequency Repetitive Transcranial Magnetic Stimulation on Upper Limb Dystonia in Patients With Wilson's Disease: A Randomized Controlled Trial

“…However, the basal ganglia are well-known to be part of a set of parallel closed circuits (basal ganglia-thalamic- cortical-basal ganglia) that originate in the cerebral cortex, cross the thalamus, and return to their respective frontal lobe origin ( 35 ). Notably, some WD patients have cerebral cortex damage ( 36 ). Thus, even though the direct effects of the TMS may be limited to the cerebral cortex, stimulation of this cortical region, if it is part of the basal ganglia circuitry, can affect the activity of these circuits and produce clinical effects.…”

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“…WD patients present with hepatic, neurologic, psychiatric or mixed symptoms. Some patients also show atypical features (Aggarwal, Bhatt 2020). Classical diagnostic indications include copper deposition in the descemet's membrane of cornea (Kayser-Fleischer Ring), low serum ceruloplasmin (< 20 mg dL -1 ) and high 24-h urinary copper excretion (> 100 μg 24 h -1 ).…”

“…and can lead mostly normal life only if detected at an early stage (Ferenci, Roberts 2012). Various aspects of diagnosis and clinical management of WD have been described in a number of recent articles (Członkowska et al 2018;Roberts 2018;Aggarwal, Bhatt 2020;Moini et al 2021).…”

“…Patients may also present with mixed symptoms with variable endophenotypes. Even after a century of the clinical description of WD by neurologist Dr. Samuel Alexander Kinnier Wilson (Wilson 1912), it remains unclear as to why some Wilson disease patients develop predominantly hepatic disease while others develop neurological disease (Hedera 2019;Aggarwal, Bhatt 2020). The genotypephenotype correlation has been the subject of investigation in several studies.…”

Initial Assessment Findings in Patients With Confirmed Wilson’s Disease

“…Вызвана гомозиготными или компаундными гетерозиготными мутациями гена ATP7B, описано более 800 мутаций, ассоциированных с БВК. Манифестирует заболевание широким спектром симптомов со стороны печени (от отклонения лабораторных тестов до клинических проявлений цирроза печени, его осложнений и острой печёночной недостаточности), неврологических нарушений, может протекать и бессимптомно [2,3,4].…”