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or '''hepatolenticular degeneration''' is an
Autosomal Recessive Hereditary Disease , with an incidence of about 1 in 30,000 in most parts of the world and a male preponderance. Its main feature is accumulation of
Copper in
Tissues , which manifests itself with
Neurological symptoms and
Liver disease. The estimated
Heterozygous Carrier rate is about 1 in 100, meaning that 1 in 100 people are unaffected carriers of this
Mutation .
Symptoms usually appear around the ages of 10 to 21 years, but sometimes not until the age of 30, and in rare instances at age 50 and even beyond. Presentation before 5 years of age is extremely rare, despite the biochemical defect being present at birth.
The age of presentation seems to correlate with the organ system involved. About half (40–50%) of patients first present with hepatic symptoms and half (40–50%) with neurologic symptoms. The average age for hepatic symptoms is 10–14 years, compared with 19–22 years for neurologic symptoms. Patients rarely present after age 40.
The main features are liver and neuropsychiatric problems. . Neuropsychiatric phenomena are early
Dementia ,
Mood Disorder s or
Psychosis and signs of
Asterixis (a flapping
Tremor of the hands) and
Parkinsonism (including
Ataxia ,
Dyskinesia , and
Rigidity ).
Adjunctive features are
Renal (
Renal Tubular Acidosis ,
Kidney Stones ),
Ophthalmic (
Kayser-Fleischer Ring s, sunflower
Cataract s),
Cardiac (
Cardiomyopathy ,
Cardiac Arrhythmia s) and
Dermal (
Hidradenitis Suppurativa ).
Hemolysis (anemia due to destruction of red blood cells) is usually present only in severe cases.
A suppressed level of
Ceruloplasmin is present in over 80% of patients, and this is commonly performed as a screening test in patients with liver problems. A more accurate measurement is the direct testing for copper levels in a 24h specimen of urine, in the
Blood or in the sample obtained by
Liver Biopsy . The average concentration of hepatic copper may reach 20 times normal levels, whilst plasma
Ceruloplasmin levels are typically less than 30% of normal.
An eye exam would detect the
Kayser-Fleischer Ring , although its absence does not rule out Wilson's and it may be missed on cursory examination. This sign is characterised by brown rings around the cornea in the eye that result from copper deposition in
Descemet's Membrane of the
Cornea . Wilson's disease is also associated with sunflower cataracts, brown or green pigmentation of the anterior and posterior lens capsule.
The ''Wilson disease gene'' (''
ATP7B '') has been mapped to
Chromosome 13 (13q14.3) and is expressed primarily in the liver,
Kidney , and
Placenta but has also been found in the
Heart ,
Brain , and
Lung , albeit at much lower levels. The gene codes for a P-type
ATPase that transports copper into
Bile and incorporates it into
Ceruloplasmin .
The mutant form of ''ATP7B'' expressed in people with Wilson's disease inhibits the release of copper into bile. As the excretion of copper from the body is thus impaired, the copper builds up in the liver and injures liver tissue. Eventually, the damage causes the liver to release the copper directly into the bloodstream, which carries the copper throughout the body. The copper buildup leads to damage in the kidneys, brain, and eyes, presumably by generation of .
Copper deposits in the
Basal Ganglia , particularly in the
Putamen and
Globus Pallidus (together called the ''
Lenticular Nucleus ''), result in cell death, producing symptoms akin to
Parkinson's Disease .
The disease is treated with lifelong use of
Chelating Agents such as D-
Penicillamine or
Trientine Hydrochloride ,
Drug s that help remove copper from
Tissue . Patients will also need to take
Vitamin B6 and follow a low-copper diet, which means avoiding
Mushroom s,
Nuts ,
Chocolate , dried
Fruit , liver, and
Shellfish .
Taking extra
Zinc may be helpful in blocking the
Intestine s' absorption of copper. Zinc acetate is an agent utilized to inhibit copper absorption in patients with Wilson's disease. It blocks the intestinal absorption of the metal both from the diet and endogenous secretions. It also acts by producing metallothionein, a protein that binds with copper to prevent its release into the blood, and facilitates elimination via the stool.
Liver Transplantation is effective in patients with fulminant Wilson disease that does not respond to the usual treatment. Because the primary defect resides within the liver, transplantation is curative, but as it is only undertaken in severely ill patients the prognosis is still mediocre.
In Western populations the incidence is around 1 per 30,000, with a carrier rate of 1 in 100. The gene frequency is much higher in Hispanics, especially in Central America, and in El Salvador, the incidence is 1 in 186. In
Usulután Department , El Salvador it has been reported that 1 in 7 persons carry the disease.
The disease bears the name of the , was discovered in 1956 by Dr John Walshe.Walshe JM. Penicillamine, a new oral therapy for Wilson's disease. ''Am J Med'' 1956;21:487-95. PMID 13362281. The genetic basis was elucidated in the 1980s and 1990s by several research groups.Tanzi RE, Petrukhin K, Chernov I, Pellequer JL, Wasco W ''et al'', Ross B, Romano DM, Parano E, Pavone L, Brzustowicz LM, et al. The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene. ''Nat Genet'' 1993;5:344-50. PMID 8298641.Bull PC, Thomas GR, Rommens JM, Forbes JR, Cox DW. The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene. ''Nat Genet'' 1993;5:327-37. PMID 8298639.
''Original text is from a
Public Domain source found at: http://www.niddk.nih.gov/health/digest/summary/wilson/wilson.htm ''
