Wilson Disease

Abstract

The clinical manifestations of Wilson disease (WD) are varied and challenging. We conducted the current study to present the phenotypic characteristics and follow-up for a large cohort of patients with WD. We reviewed the medical records of 282 cases of WD (male:female ratio, 196:86) for clinical features, investigations, treatment, and outcome data. The clinical presentations were as follows: hepatic, 42 (14.9%); hepato-neurologic, 10 (3.5%); neurologic, 195 (69.1%); pure psychiatric, 7 (2.4%); osseomuscular, 6 (2.1%); and "presymptomatic," 15 (5.3%). Mean age was 15.9 years. Presymptomatic patients and those with the hepatic form of WD were younger and patients with osseomuscular and psychiatric forms were older than neurologic patients. The mean duration of illness at the time of diagnosis was 28 months. Predominant neurologic features were as follows: parkinsonism, 62.3%; dystonia, 35.4%; cerebellar, 28%; pyramidal signs, 16%; chorea, 9%; athetosis, 2.2%; myoclonus, 3.4%; and behavioral abnormalities, 16%. Kayser-Fleischer (KF) rings were seen as follows: neurologic patients, 100%; hepatic patients, 86%; and presymptomatic patients, 59%. Positive family history was noted in 47% and consanguinity in 54%. Patients born of consanguineous parents had an earlier age of onset and shorter duration of illness before presentation. Serum ceruloplasmin was decreased in 93% and 24-hour urinary copper excretion was increased in 70% of patients. Neuroimaging (computed tomography/magnetic resonance imaging) and electrophysiologic abnormalities were seen in many patients. Overall, 195 patients were on D-penicillamine therapy and 182 on zinc sulphate. Follow-up data, available for 225 patients, for a mean duration of 46 months, revealed improvement in 176, no change in 20, and deterioration in 6. Twenty-three patients died. To conclude, despite increased awareness and recognition and significant inroads into therapeutic frontiers, follow-up remains poor in developing countries and a return to previous level of functioning is not universal.

Copper·Dopamine Complex Induces Mitochondrial Autophagy Preceding Caspase-independent Apoptotic Cell Death

“…The accumulation of copper in liver results in copper overload in the brain, inducing neurological Wilson disease. A study on the clinical presentations of this disease (282 cases) showed that 69% of patients were classified as having neurological Wilson disease (50). The predominant neurological features were Parkinsonism, 62.3%; dystonia, 35.4%; cerebellar, 28%; pyramidal signs, 16%; chorea, 9%; athetosis, 2.2%; myoclonus, 3.4%; and behavioral abnormalities, 16% (50).…”

“…A study on the clinical presentations of this disease (282 cases) showed that 69% of patients were classified as having neurological Wilson disease (50). The predominant neurological features were Parkinsonism, 62.3%; dystonia, 35.4%; cerebellar, 28%; pyramidal signs, 16%; chorea, 9%; athetosis, 2.2%; myoclonus, 3.4%; and behavioral abnormalities, 16% (50). The fact that Parkinsonism is one of the major neurological symptoms in Wilson disease opens the question as to why the copper overload effect is specific for dopaminergic neurons.…”

Wilson’s disease: A review of what we have learned

“…Neurological manifestations can be categorized as: (1) an akinetic-rigid syndrome similar to Parkinson's disease; (2) pseudosclerosis dominated by tremor; (3) ataxia; and (4) a dystonic syndrome, which often leads to severe contractures [33,34] . Neuropsychiatric symptoms and signs, including decrease in scholastic performance, hand-eye discoordination, and behavioral changes may foretell a more florid neuro logical presentation [35] . Other findings include drooling, spasticity, chorea, athetosis, myoclonus, micrographia, dyslalia, hypomimia, and dysarthria [35,36] .…”

“…Neuropsychiatric symptoms and signs, including decrease in scholastic performance, hand-eye discoordination, and behavioral changes may foretell a more florid neuro logical presentation [35] . Other findings include drooling, spasticity, chorea, athetosis, myoclonus, micrographia, dyslalia, hypomimia, and dysarthria [35,36] . Ocular mani festations include the KayserFleischer ring and sunflower cataracts in the lens, deposition of copper in the Descemet's membrane in the first case, and in the anterior and posterior capsule of the lens, sparing epithelial and cortical cells, in the latter [37,38] .…”

Single Pass Albumin Dialysis and Plasma Exchange for Copper Toxicity in Acute Wilson Disease

“…Clinical manifestations predominantly reflect hepatic injury, but also include neuropsychiatric manifestations and hemolytic anemia [2]. A diagnosis of WD is supported by low ceruloplasmin, elevated hepatic copper, increased urinary copper excretion, and detection of Kayser-Fleischer rings on ophthalmologic examination [3].…”