Long-term follow-up of Wilson disease: natural history, treatment, mutations analysis and phenotypic correlation.
OBJECTIVE
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.
Bruha
Radan
R
4th Department of Internal Medicine, 1st Faculty of Medicine, Charles University in Prague, General Teaching Hospital, Prague, Czech Republic. bruha@cesnet.cz
Marecek
Zdenek
Z
Pospisilova
Lenka
L
Nevsimalova
Sona
S
Vitek
Libor
L
Martasek
Pavel
P
Nevoral
Jiri
J
Petrtyl
Jaromir
J
Urbanek
Petr
P
Jiraskova
Alena
A
Ferenci
Peter
P
D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D058070:Asymptomatic Diseases; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D002614:Chelating Agents / Q000378:metabolism; D016009:Chi-Square Distribution; D003300:Copper / Q000378:metabolism*; D000073840:Copper-Transporting ATPases; D018153:Czech Republic; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006527:Hepatolenticular Degeneration / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010396:Penicillamine / Q000627:therapeutic use; D010641:Phenotype; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult; D019345:Zinc Acetate / Q000627:therapeutic use; D019287:Zinc Sulfate / Q000627:therapeutic use
D027682:Cation Transport Proteins; D002614:Chelating Agents; D019287:Zinc Sulfate; D003300:Copper; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases; D019345:Zinc Acetate; D010396:Penicillamine