Abstrakt
Background & Aims: 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 mu g/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.