Wilson Disease

Wilson's disease is a genetic disorder of copper metabolism, leading to an excessive accumulation of copper in certain tissues and organs, including the liver, brain, kidneys, and/or corneas of the eyes. Without prompt, appropriate treatment, the disorder may result in progressive liver disease, degenerative changes of the brain, psychiatric abnormalities, and other findings.

Generally, the younger the age at symptom onset, the greater the degree of liver (hepatic) involvement. Associated findings may include enlargement of the liver (hepatomegaly), acute or chronic liver inflammation (hepatitis), scarring and impaired functioning of the liver (cirrhosis), and other complications.

Neurologic signs of Wilson's disease appear to predominate in those with symptom onset after age 20. Such neurologic signs typically become apparent in the second or third decade of life, although they may appear as late as the sixth decade. These findings may include dystonia; muscle stiffness (rigidity); tremor; impaired coordination of certain voluntary movements (ataxia); "swaying" of the head (head titubation); increasingly impaired articulation of speech (dysarthria); and/or other findings. Dystonia involving muscles of the face, tongue, and throat (pharynx) may cause or contribute to dysarthria and may lead to additional findings, such as an unusual whispering quality to the voice ("whispering" dysphonia), drooling, and/or a fixed grinning expression (risus sardonicus). In addition, dystonic movements and abnormal postures may affect muscles of the arms, legs, and trunk. Some patients may also develop cognitive changes, resulting in increasing irritability, anxiety, severe depression, unusual behaviors, or other psychiatric problems. Additional findings associated with Wilson's disease may include the presence of distinctive, golden brown rings at the outer margins of the corneas (Kayser-Fleischer rings); premature destruction of red blood cells, leading to decreased levels of the oxygen-carrying component of the blood (hemolytic anemia); and/or progressive kidney failure.

Wilson's disease is inherited as an autosomal recessive trait. The disorder results from changes (mutations) in a gene, known as ATP7B, located on chromosome 13 (13q14.3). The ATP7B gene regulates production of a protein that plays a role in the transport of copper (copper-transporting ATPase). Although the specific underlying defect in Wilson's disease is unknown, some researchers suggest that it may be related to the body's inability to produce sufficient levels of ceruloplasmin, an enzyme in the fluid portion of the blood that binds to copper and is involved in its transport and regulation. In patients with neurologic signs of the disease, such findings are thought to result from progressive involvement of certain regions of the basal ganglia.

	Neuroacanthocytosis