Wilson disease (WD) or hepatolenticular degeneration is an inherited disorder of copper metabolism characterised by pathological copper accumulation in many organs, particularly the liver and brain, leading to a wide range of symptoms.
The disease bears the name of the British physician Samuel Alexander Kinnier Wilson (1878–1937), a neurologist who described the condition, including the pathological changes in the brain and liver, in 1912. Wilson’s work had been predated by, and drew on, reports from German neurologist Carl Westphal (in 1883), who termed it “pseudosclerosis“; by the British neurologist William Gowers (in 1888); and by Adolph Strümpell (in 1898), who noted hepatic cirrhosis. Neuropathologist John Nathaniel Cumings made the link with copper accumulation in both the liver and the brain in 1948. The occurrence of hemolysis was noted in 1967.
Homozygous or compound heterozygous mutations ATP7B gene ↓ Defective ATP7B copper-binding protein Mediates the excretion of copper into bile & Delivers copper for functional synthesis of ceruloplasmin (major copper-containing protein in the blood) ↓ Copper overload (in liver, brain and other organs)
The liver has the highest tissue expression of the ATP7B copper transporter and is the central organ regulating systemic copper balance. Impairment of copper biliary excretion caused by ATP7B dysfunction leads to hepatic copper accumulation. Liver injury is, therefore, the earliest and most frequent manifestation of WD.
First clinical manifestation (40–60%)
Acute hepatitis, acute-on-chronic liver failure, and cirrhosis
Coomb’s negative hemolytic anaemia, with transient episodes of low-grade hemolysis and jaundice (free Cu damages RBCs)
Wing beating tremor (characteristic sign, up to 55%): Can be resting, postural or kinetic and may start initially as unilateral or bilateral tremor with mainly distal upper extremities involvement and may eventually involve entire body
Dystonia (10-65%): Abnormal posture of various body segments commonly associated with twitching or twisting movements
Risus sardonicus (abnormal facial expression presenting as a fixed smile due to dystonia of the risorius muscle)
Parkinsonism (19–62%): Symmetric bradykinesia, rigidity, hypomimia, gait and posture disturbances as well as dysarthria, dysphagia and drooling
Ataxia (30%): Symptom of cerebellar dysfunction (ataxic gait and posture, impaired coordination, intentional tremor, dysarthria) usually in combination with other movement disorders
Chorea (rare, 6–16%): Rapid, irregular involuntary movements of face, head, trunk or extremities
Gait & posture disturbances (44–75%)
Impaired handwriting (57%): Often as an early sign of the disease
Dysarthria (M/C neurological symptom, 97%)
Clinical subtypes: 1) cerebellar; 2) extrapyramidal (dystonic, parkinsonian) and 3) mixed (unclassified due to symptoms overlapping)
Dysphagia (50%): Difficulties in any phase of swallowing (oral preparation, oral transit, swallowing, drooling)
Complications: Bronchoaspiration, pneumonia, malnutrition and weight loss.
Drooling (classic neurological symptom of WD, 68%): Result of dysphagia or orofacial dystonia.
Kayser-Fleischer ring (100% neurological , 40–50% of hepatic and 20–30% presymptomatic WD cases): Golden, brown or green colouration at the periphery of the cornea)
Due to copper deposition in Descemet’s membrane
Sunflower cataracts in lens (rare, 2-20%): Central disc with radiating petal-like fronds located under the lens capsule
Copper deposition in anterior & posterior capsule of lens, sparing epithelial and cortical cells
Mostly secondary to the somatic and brain pathology of the disease.
Depression (20–60%), with a high rate of suicidal attempts (4–16%)
Bipolar disorder (14–18%)
Lesions of frontal lobe or its pathways: Emotional lability, irritability and aggression, shallow cheerfulness, euphoria, social disinhibition, hypersexuality, lack of criticism and deficits in planning and anticipating social consequences
Psychosis (more often in patients with neurological symptoms):
Behavioural and personality disorders:
Most common manifestations: Irritability, aggression, and antisocial behaviour