Disease of Wilson

The disease of Wilson is a secondary Genetic disease with an accumulation of Cuivre in the organization and appearing by attacks of the Foie and nervous system.

History

The disease was described for the first time by Kinnier Wilson in 1912. The responsible gene was identified at the end of the years 1980.

Before the years 1950, it was constantly mortal. The first treatments appeared about this time, initially the Dimercaprol, then the Pénicillamine in 1956, the Trientine at the end of the years 1960. The use of zinc dates from the beginnings of the year 1960.

Epidemiology

The frequency of this disease is very weak: 1 out of 30.000 to 100.000 births

Mechanism

It is due to an anomaly of a gene which intervenes in the metabolism of copper. The disease of Wilson is a Genetic disease with recessive autosomic transmission: two parents being simply healthy carriers of this gene.

The abnormal Gène is located on the Chromosome 13. 1% of the general population is carrying abnormal gene (healthy carriers hétérozygotes). It is mainly expressed in the liver and the kidneys.

This gene, named ATP7B , code a transmembrane protein of type ATPase, called ATP7B, intervening in transport will intra and extra cellular copper, making it possible to control the concentration of this metal and its excretion in the bile. If the protein is defective, metal accumulates then inside the cells.

There exists nearly 300 described changes of this gene but only, a handle of these last is responsible for the main part of the cases of disease of Wilson. The type of change also depends on the ethnic origin of the patient.

Brain

the neurological or psychiatric signs concern nearly 50% of the patients reaches disease of Wilson.

Psychiatry

The disease can appear by cognitive disorders, disorders of mood, even a Psychose.

Neurology

The attack can comprise:

a Ataxia;
of the Dyskinésie S;
a rigidity similar to that of the Parkinson's disease;
of the tremors.

Eye

The Anneaux of Kayser-Fleischer are typical disease, consistent in a discrete coloring clear chestnut of the circumference external of the secondary cornea with the copper deposits in the Membrane of Descemet. A similar aspect (but without metal deposition) can be seen however in other forms of cirrhosis.

A cataract is a traditional complication. It is characterized by an aspect spangled.

Other attacks

It can exist osseous or articular attacks. The renal attack is rare, including/understanding a tubular acidosis or a renal lithiasis.

The cardiac attack is also rare, at least in their clinical expression. Cardiomyopathie as of the Troubles of the cardiac rhythm were described.

A traditional sign is the bluish aspect of the lunule of the nails.

Diagnosis

The rate of Caeruloplasmine blood (protein comprising of copper in its center) is low, even ploughed up.

The proportioning of the copper contents of hepatic fabric is a good examination (it is increased at the time of a disease of Wilson) but requires to recourrir with a Biopsie liver. In some cases, however, this concentration can be normal (in particular in the event of advanced hepatic fibrosis).

The urinary copper excretion is increased at the time of the disease, but there exists a certain number of false-positives. Its measurement can be sensitized in the child by the administration of Pénicillinamine.

These examinations can be disturbed at the hétérozygotes (thus not presenting the disease since it is recessive).

The blood test makes it possible to also make the diagnosis of the forms pre-private clinics i.e. before the appearance of the signs of the disease which can put tens of years before appearing.

In rule, the genetic identification is not essential in the typical cases to make the diagnosis of it. It can be useful in the doubtful cases.

Treatment

The objective of the treatment is of éradiquer the toxicity of the copper deposits. The treatment must be followed to life. It should never be stopped. It consists in taking Médicament S Chélateur S which decrease the absorption of copper in the organization, or increasing the excretion of metal. The treatment has life must then be subjected to a periodic monitoring, in order to locate the appearance of annoying side effects.

Various types of drugs are employed:

the Pénicillamine increases the urinary excretion of copper. It has a recognized effectiveness but its side effects tend to make it replace by other molecules.
the Trientine which is chelating copper, tolerated often better than the pénicillamine;
ammonium tetrathiomolybdate, absorbed with the food, is fixed with the ions coppers in the digestive tract, preventing their absorbtion.
the Zinc activates an enzyme, the métellothionéine, which will fix copper in the cells of the wall of the intestine (Entérocyte S) preventing the passage of this ion in blood circulation.

A mode low in copper is recommended: it is advised to avoid the mushrooms, the seafood, the liver, as well as the chocolate.

In the extremely serious cases of fulminant hepatitises or in the gravely hurts primarily hepatic, a hepatic Transplantation can be proposed.

The genetic Council

It is necessary to carry out a detection of the disease in all the brothers and sisters of a patient at whom one has just diagnosed the disease of Wilson. The disease being of recessive transmission, probability that a brother or that a sister is reached is of 1/4. All the difficulty consists in distinguishing a form homozygote for the moment quiet but which can appear in the years or the decades which follow and a completely benign form hétérozygote.

Diagnosis anténatal

Sources

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