Current Management of Neurological Wilson's Disease

Abstract

Wilson's disease (WD) is a disorder of copper metabolism due to variants in the ATP7B gene. This autosomal recessively inherited disorder is characterized by the accumulation of copper in various body parts, mainly the liver, brain, and kidneys. Initially, WD was described to involve the hepatic and neurological systems. Subsequently, diverse presentations have been reported with skeletal and hematological manifestations and various constellations of symptoms. Neurological manifestations of WD are varied, ranging from asymptomatic neurological state to refractory dystonia. Earlier, the diagnosis was based only on measuring serum ceruloplasmin levels, urinary copper levels, and imaging. Advanced genetic testing has provided an additional mode of diagnosis in the patient, screening of the family members and, a way to better understand the genotype-phenotype associations of the disease if there are any. In the last few decades, the treatment of WD has evolved from symptomatic treatment and chelation therapy to many new advanced measures for both copper chelation and symptomatic relief. With a better understanding of the genetic aspects of WD in recent years, there has been more focus on gene therapy, novel therapies targeting ATP7B genes, and therapies targeting mutant proteins to prevent copper accumulation. This article highlights the advances in diagnostic methods and treatment modalities in WD.

Keywords: Movement disorders; Neurological and/or hepatic WD; Outcome; Treatment; Wilson’s disease.

Figure 1

Algorithm showing the approach to a suspected Wilson’s Disease patient. MRI: Magnetic resonance imaging; WD: Wilson disease.

Figure 2

A to C- MRI axial sections of Case-1 depicting T2 hyperintensities in bilateral thalamus (A), face of the giant panda sign in the midbrain (B), and face of the miniature panda sign in the pons (C). MRI: Magnetic resonance imaging.

Figure 3

Algorithm for screening of asymptomatic siblings of Wilson’s Disease patient. KF ring: Kayser–Fleischer ring; MRI: Magnetic resonance imaging; WD: Wilson disease.