Wilson's Disease

Danielle & Rachael


Nature of the Genetic Difficulty

Wilson's disease or hepatolenticular degeneration is an autosomal recessive genetic disorder in which copper accumulates in tissues; this manifests as neurological or psychiatric symptoms and liver disease. It is treated with medication that Pic1234.jpgreduces copper absorption or removes the excess copper from the body, but occasionally a liver transplant is required.
The condition is due to mutations in the Wilson disease protein gene. A single abnormal copy of the gene is present in 1 in 100 people, who do not develop any symptoms (they are carriers). If a child inherits the gene from both parents, they may develop Wilson's disease. Symptoms usually appear between the ages of 6 and 20 years, but cases in much older people have been described. Wilson's disease occurs in 1 to 4 per 100,000 people.Wilson's disease is named after Samuel Alexander Kinnier Wilson (1878–1937), the British neurologist who first described the condition in 1912.
The Wilson's disease gene has been mapped to chromosome 13 and is expressed primarily in the liver, kidney, and placenta. The gene codes for a P-type (cation transport enzyme) ATPase that transports copper into bile and incorporates it into ceruloplasmin.Mutations can be detected in 90%. Most (60%) are homozygous for ATP7B mutations (two abnormal copies), and 30% have only one abnormal copy. Ten per cent have no detectable mutation.

Basis Facts of Disease

The main sites of copper accumulation are the liver and the brain, and consequently liver disease and neuropsychiatric symptoms are the main features that lead to diagnosis.People with liver problems tend to come to medical attention earlier, generally as children or teenagers, than those with neurological and psychiatric symptoms, who tend to be in their twenties or older. Some are identified only because relatives have been diagnosed with Wilson's disease; many of these, when tested, turn out to have been experiencing symptoms of the condition but haven't received a diagnosis.

Symptoms

Abnormal posture of arms and legs
Confusion or delirium
Dementia
Difficulty moving arms and legs, stiffness
Difficulty walking (ataxia)
Emotional or behavioral changes
Enlargement of the abdomen (abdominal distention)
Personality changes
Phobias, distress (neuroses)
Slow movements
Slow or decreased movement and expressions of the face
Speech impairment
Tremors of the arms or hands
Uncontrollable movement
Unpredictable and jerky movement
Vomiting blood
Weakness
Yellow skin (jaundice) or yellow color of the white of the eye (icterus)


Prognosis

The goal of treatment is to reduce the amount of copper in the tissues. This is done by a procedure called chelation -- certain medications can bind to copper and help remove it through the kidneys or gut. Treatment must be lifelong.
The following medications may be used:
Penicillamine (Cuprimine, Depen) binds to copper and leads to increased release of copper in the urine.
Trientine (Syprine) binds (chelates) the copper and increases its release through the urine.
Zinc acetate (Galzin) blocks copper from being absorbed in the intestinal tract.
Vitamin E supplements may also be used.

Sources Cited

http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001789/