Wilson’s Disease

Wilsons Disease (Hepatolenticular Degeneration
Lenticular Degeneration, Progressive
is an inherited (autosomal recessive), genetic disorder in which copper builds up in the liver and is released into other parts of the body, eventually causing damage to the liver and brain .
The disease should be considered by any physician investigating any obscure neurological or psychiatric symptoms.

The age of onset is from four upwards, but liver problems are more obvious in the younger
presenting children. Sometimes a family history of young children dying of or suffering from cirrhosis (liver failure) will suggest the disease in a child with no liver problems; the disease is inherited. It is quite rare, but definitely happens, for children to have a purely neurological or behavioral presentation; when copper has been deposited in the
ecerebral cortex there may be behavioral symptoms something like PDD/psychosis, or behavior disorders, or in middle childhood more neurological symptoms begin which can imitate cerebral palsy or multiple sclerosis; a tremor is very characteristic, may cause fine motor problems and has been mistaken for learning disability.

A little more than half of all patients with WD first show symptoms of hepatitis. In addition, those who have liver-related symptoms first, do so at a younger age than do those who first present with neuropsychiatric symptoms-15 years and 25 years on average, respectively. However, the symptoms and their severity are quite variable, and the diagnosis of WD has been made in children as young as three years old, and in adults in their 60s.

Neurological symptoms are primarily the result of copper’s toxic effects in the basal ganglia, a portion of the brain that controls some of the subconscious aspectsuntary movement such as accessory movements and inhibiting tremor. These symptoms include:

Dystonia. Prolonged muscular contractions that may cause twisting (torsion) of body parts, repetitive movements, and increased muscular tone.
Dysarthria. Difficulty in articulating words, sometimes accompanied by drooling.
Dysphagia. Difficulty swallowing.
Pseudosclerosis. Symptoms similar to multiple sclerosis.

There may be a family history of liver disease or perhaps an enlarged liver in a Wilson’s Disease patient.
Clinical symptoms rarely develop before 5 years of age, despite the biochemical defect being present at birth.

Symptoms usually appear around the ages of 18 to 21 years, but sometimes not until the age of 30, and in rare instances up to age 50. The most classical sign are the Kayser-Fleischer rings (brown rings around the cornea in the eye) [Bruno Fleischer, German ophthalmologist ; Bernhard Kayser, German ophthalmologist; Ernst Adolf Gustav Gottfried von StrÃ?¼mpell, German neurologist] that result from copper deposition in Descemet’s membrane of the cornea. Other signs depend on whether the damage occurs in the liver, blood, central nervous system, urinary system, or musculoskeletal system. Many signs would be detected only by a doctor, like swelling of the liver and spleen; fluid buildup in the lining of the abdomen; anemia; low platelet and white blood cell count in the blood; high levels of amino acids, protein, uric acid, and carbohydrates in urine; and softening of the bones. Some symptoms are more obvious, like jaundice, which appears as yellowing of the eyes and skin; vomiting blood; speech and language problems; tremors in the arms and hands; and rigid muscles.

The easiest biochemical test is measurement of ceruloplasmin, a blood protein that is nearly always decreased in patients with WD. While low levels of ceruloplasmin are highly suggestive, a liver biopsy to detect excess copper levels is much more accurate. Testing for mutations in the ATP7B gene is nearly definitive, but the large number of mutations catalogued in the gene means that only certain individuals may benefit from testing. A consultation with a genetics professional is always recommended.

A gastroenterologist will treat and monitor liver disease, while a neurologist and psychiatrist (or neuropsychiatrist) should evaluate and treat neuropsychiatric symptoms. Since many individuals achieve remission of their neurologic symptoms once treatment is started, neuropsychiatric consultations may only be short term. If necessary, periodic consultations with a geneticist can provide updated information on genetic testing.

The important thing
about Wilsons disease (named after Samuel Alexander Kinnier Wilson (1877-1937), British neurologist in 1912) is
that it is TREATABLE. Various tests are needed to make the diagnosis,
caeruloplasmin and various copper levels.

The disease is treated with lifelong use of chelating agents such as D-penicillamine, trientine hydrochloride, or Galzin (Zinc Acetate), drugs that help remove copper from tissue. Patients will also need to take vitamin B6 and follow a low-copper diet, which means avoiding mushrooms, nuts, chocolate, dried fruit, liver, and shellfish. Taking extra zinc may be helpful in blocking the intestines’ absorption of copper. However only 0.4% of the cases are actually treatable.

Liver transplantation is effective in patients with fulminant Wilson’s disease that does not respond to the usual treatment.

The disease bears the name of the British physician Dr Samuel Alexander Kinnier Wilson (1878-1937), who described the condition in 1912. Dr J.N. Cumings made the link with copper accumulation in 1948. The first effective chelation agent, penicillamine, was discovered in 1956 by Dr John Walshe. The genetic basis was elucidated in the 1980s and 1990s by several research groups.

Further information is available through:

Wilson’s Disease Association. 4 Navaho Drive, Brookfield, CT 06804-3124. (800) 399-0266; Fax: (203) 775-9666. http://www.wilsondisease.org.

National Center for the Study of Wilson’s Disease. 432 West 58th Street, Suite 614, New York, NY 10019. (212) 523-8717; Fax: (212) 523-8708.

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