Late-onset Wilson's disease.
OBJECTIVE
The clinical symptoms and age at onset of Wilson's disease (WD) are highly variable. This study investigated patients who became symptomatic at >40 years of age.


METHODS
Clinical features, laboratory data, and mutation analysis were evaluated in 46 (3.8%) of 1223 patients who were investigated in a multinational study on genotype-phenotype correlations (1053 index patients, 170 siblings) who were >40 years of age at onset of symptoms and, in 2 asymptomatic siblings, diagnosed at >40 years of age.


RESULTS
Thirty-one patients presented with neurologic symptoms (mean age, 44.5 years; range, 40-52; male/female, 14/17), 15 presented with liver disease (mean age, 47.1 years; range, 40-58; male/female, 6/9), and 2 were asymptomatic siblings. Hepatic copper content was measured in 17 patients and was above 250 microg/g dry weight in 13. One patient with hepatic presentation had "fulminant" WD, the remaining 14 abnormal liver function tests and/or hepatomegaly. Liver biopsy specimens were available in 13 patients presenting with liver disease (cirrhosis, 10; chronic hepatitis, 2; steatosis, 1; no abnormalities, 1) and in 14 neurologic patients (cirrhosis, 9; advanced fibrosis, 1; chronic hepatitis, 2; no abnormalities, 2). Twenty-seven of the 46 index cases had mutations on both chromosomes (including 13 H1069Q/H1069Q), 13 on just 1 chromosome.


CONCLUSIONS
Late-onset WD is a frequently overlooked condition. The diagnostic features and the frequency of late-onset WD gene mutations were not different than in patients with an earlier onset of disease. Factors other than ATP7B mutations may modify the phenotypic presentation of WD.
Ferenci
Peter
P
Department of Internal Medicine III, Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria. peter.ferenci@meduniwein.ac.at
Członkowska
Anna
A
Merle
Uta
U
Ferenc
Szalay
S
Gromadzka
Grazyna
G
Yurdaydin
Cihan
C
Vogel
Wolfgang
W
Bruha
Radan
R
Schmidt
Hartmut T
HT
Stremmel
Wolfgang
W
D000251:Adenosine Triphosphatases / Q000235:genetics*; D000328:Adult; D017668:Age of Onset; D001706:Biopsy; D027682:Cation Transport Proteins / Q000235:genetics*; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D003300:Copper / Q000378:metabolism; D000073840:Copper-Transporting ATPases; D004247:DNA / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006527:Hepatolenticular Degeneration / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors
D027682:Cation Transport Proteins; D003300:Copper; D004247:DNA; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases