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At a glance

It is an inherited disease of copper metabolism dysfunction that is characterized by cirrhosis and central nervous system (CNS) findings. The neurological clinical features include tremor, dysarthria, rigid dystonia, seizures, and psychiatric disorders. Other clinical features include acute liver failure, chronic hepatitis, cirrhosis, renal tubular acidosis, renal failure, and cardiomyopathy. It is fatal if not recognized and treated promptly. The pathognomonic sign is the presence of a Kayser-Fleischer ring, a brownish-yellow ring surrounding the corneo-scleral junction (limbus). This ring is visible especially when neurological symptoms are present. Medications used include chelating agents such as trientine and D-penicillamine, which may present significant implications with anesthesia. Zinc sulphate supplements are also frequently used. Complications include liver failure and/or cancer, as well as kidney problems.

Synonym

Hepatolenticular Degeneration.

History

It was first observed in 1854 by Friedrich Theodor von Frerichs (1819-1885), a German pathologist who practiced in Austria. The disease is named after Samuel Wilson (1878-1937), an American born-British neurologist, who described the clinical condition.

Incidence

It is reported as 1:30,000 individuals in the general population. However, it is most common amongst Eastern Europeans, Jews, Arabs, Italians, Japanese, Chinese, and Indians. Males and females are equally affected.

Genetic inheritance

It is inherited as an autosomal recessive trait. Gene localized to chromosome 13. The mutation is located on the Wilson protein (ATP7B) gene.

Pathophysiology

Caused by mutation in the ATPase, Cu2+ transporting, beta-polypeptide gene (ATP7B) located at 13lq14.3–q21.1. A defect in copper metabolism leads to decreased incorporation of copper into ceruloplasmin and reduction in biliary excretion of copper. This results in deposition of copper into liver (resulting in fatty intracellular accumulations progressing to deposition of collagen, fibrosis, and nodular cirrhosis followed by development of portal hypertension and esophageal and gastric varices), brain (particularly basal ganglia, putamen, globus and pallidus, and caudate, resulting in inflammation, gliosis, and eventually loss of neurons), and kidney (resulting in Fanconi Syndrome, aminoaciduria, glycosuria, phosphaturia, and nephrolithiasis). Other systemic involvement may include hemolytic anemia, osteoporosis, copper deposition in heart, rhabdomyolysis, and hypoparathyroidism.

Diagnosis

Based on clinical course and biochemical findings, including low serum ceruloplasmin, elevated 24-hour urinary copper excretion, and liver biopsy. Most affected individuals are diagnosed between the ages of 5 and 35. However, it is not surprising that it can also affect younger and older people as well.

Clinical aspects

Characterized by the involvement of several systems. Hepatic: a spectrum from fulminant liver failure associated with coagulopathy and encephalopathy (more common in children) to chronic progressive cirrhosis with development of portal hypertension. Neurologic: intention tremor, dysarthria, loss of fine motor control, mask-like facies, pseudobulbar involvement, drooling, dysphagia, dystonia, incoordination, difficulty with fine motor tasks, and gait disturbance. ...

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