La maladie de Wilson en 2018

Wilson's disease (WD) is characterized by deleterious copper accumulation in the liver and the brain. It is one of those rare genetic disorders that benefits from effective treatments which have dramatically transformed the prognosis. The establishment of a national reference center in 2005 that was re-certified this year and the inclusion of patients in a national registry allowed us to progress in the knowledge and management of this rare disease. In France, the clinical prevalence is estimated to 1.5/100 000 but the genetic prevalence is higher around 1/7,000. An incomplete penetrance of the gene or the presence of modifier genes may account for the difference. The clinical spectrum of WD is wider as expected with pauci-symptomatic presentations and a late onset of the disease over the age of 40 in 6 % of patients. WD is suspected when ceruloplasminemia is low and 24h-urinary copper excretion is elevated. Recently, a major diagnostic advance has been reached with the implementation of the direct dosage of toxic free copper, called exchangeable copper. The ratio of exchangeable copper/total copper (REC) > 18.5 % provides the diagnostic of WD with high sensitivity and specificity. Moreover, copper exchangeable > 2.08 μmol/L at diagnosis is indicative of the severity of the extra-hepatic (brain and retina) involvement. Treatment of WD is based on an initial active and prolonged chelating phase (by Trolovol® or Trientine®) followed by a maintenance phase with Trientine® or Zinc salt. The two major problems which may be encountered are neurological worsening during the initial phase and non-compliance to treatment during the maintenance phase. Liver transplantation is the recommended therapeutic option in WD with acute liver failure or end-stage liver cirrhosis; its indication should be considered when a rapid neurological worsening occurs despite effective chelation. Regular clinical, biological and liver ultrasound follow-up is essential to evaluate treatment efficacy, tolerance and adherence but also to detect the appearance of hepatocellular carcinoma on a cirrhotic liver. The near future is promising with the arrival of a new chelator, tetrathiomolybdate and with the development of gene therapy.