Long-term follow-up of Wilson disease: natural history, treatment, mutations analysis and phenotypic correlation

Liver Int. 2011 Jan;31(1):83-91. doi: 10.1111/j.1478-3231.2010.02354.x. Epub 2010 Oct 20.


Background and aims: Wilson disease (WD) is an inherited disorder of copper metabolism. When treated, the outcome can be excellent, although the long-term survival has yet to be well documented. The aim of this study was to describe the long-term outcome of a cohort of patients with WD and to assess those factors affecting the phenotypic manifestation of WD.

Methods: The presence of mutations to the ATP7B gene, the clinical manifestations, treatments and the long-term outcomes were analysed retrospectively in 117 patients with WD (59 men and 58 women, aged at evaluation 38.5 ± 11, range 16-63 years).

Results: Fifty-five patients with a neurological presentation, 51 patients with a hepatic presentation and 11 asymptomatic patients were followed up for an average of 15.1 ± 10 years (median 12 years, range 1-41 years). The H1069Q ATP7B gene mutation was the most frequent genetic variant (54.3%); the frequency of this mutation did not differ between patients with either the hepatic or the neurological presentation (P = 0.099). d-penicillamine or zinc salts (81 and 17% respectively) were used for treatment, and three patients underwent liver transplantation. The majority of symptomatic patients became asymptomatic, or improved, during the follow-up (82% patients with hepatic presentation, 69% with neurological presentation). The long-term survival of patients with WD did not differ from that of the general Czech population (P = 0.95).

Conclusions: Long-term follow-up shows a satisfactory response in the great majority of adequately treated patients with WD and survival coincides with that of the general population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics*
  • Adenosine Triphosphatases / metabolism
  • Adolescent
  • Adult
  • Asymptomatic Diseases
  • Cation Transport Proteins / genetics*
  • Cation Transport Proteins / metabolism
  • Chelating Agents / metabolism
  • Chi-Square Distribution
  • Copper / metabolism*
  • Copper-Transporting ATPases
  • Czech Republic
  • DNA Mutational Analysis
  • Disease Progression
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Hepatolenticular Degeneration / enzymology
  • Hepatolenticular Degeneration / genetics*
  • Hepatolenticular Degeneration / mortality
  • Hepatolenticular Degeneration / therapy
  • Humans
  • Kaplan-Meier Estimate
  • Liver Transplantation
  • Male
  • Middle Aged
  • Mutation*
  • Penicillamine / therapeutic use
  • Phenotype
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome
  • Young Adult
  • Zinc Acetate / therapeutic use
  • Zinc Sulfate / therapeutic use


  • Cation Transport Proteins
  • Chelating Agents
  • Zinc Sulfate
  • Copper
  • Adenosine Triphosphatases
  • ATP7B protein, human
  • Copper-Transporting ATPases
  • Zinc Acetate
  • Penicillamine