Article

Texts published, in 1912, 100 years ago, by Sir K. Wilson on his eponymous
disease in Brain, The Lancet and La Revue Neurologique highlight the relevance of
his descriptions in the light of the current knowledge. Wilson's invocation of an
"unknown toxin" appears today as a prophetic intuition as the presence of excess
copper in the liver was mentioned for the first time a year later whereas the
role of copper in this disease was not described until 1929. Progress has been
made to better understand the physiology of Wilson's disease (WD). The ATP7B gene
implicated in WD is located on chromosome 13 and more than 500 mutations and 100
polymorphisms have been to date identified. The phenotypic expression is highly
variable, even within a family. This can partly be explained by environmental
factors as nutrition. Modulator genes are also involved in the phenotypic
expression of the disease. Most of symptoms observed in WD have already been
described in detail by Wilson in 1912, but subsequent progress was made over the
following 100 years, helping the physician diagnose WD. Hepatic and neurological
symptoms are the most frequent expressions of the disease. Other extrahepatic
features include renal manifestations, osteoarticular disorders, myocardial
abnormalities, endocrine disturbances, realizing a multisystemic disease. The
diagnosis of the disease is based on a combination of clinical symptoms,
biological, radiological and genetic data and new tools (Brain MRI, relative
exchangeable copper...) allow reducing delay to diagnosis. Therapeutic findings
have also changed the disease prognosis. Treatment is based on the use of copper
chelators to promote copper excretion from the body (D-penicillamine and
Triethylenetetramine) and zinc salts to reduce copper absorption.
Tetratiomolybdate appears to be a promising treatment. While significant progress
has been made during this century, many physiological aspects of this disease
remain unknown and require further research to find answers in the next 100
years.
CI - Copyright (c) 2013 Elsevier Masson SAS. All rights reserved.

Langue : ANGLAIS