Different clinical presentation of Wilson's disease in identical twins

Introduction: Wilson's disease (WD) is a rare autosomal recessive disease caused by mutation of the ATP7B gene. The toxic accumulation of copper in many organs is fatal without treatment. The diagnosis may be difficult because of vide variability of symptoms. Only few papers are available on identical twins with WD. Here we report on identical twins with different clinical presentation. Case report: 21-year-old female university student went to see the doctor because of abdominal discomfort, nausea and vomiting. Liver cirrhosis was diagnosed. The cause of the liver disease was not identified that time. Symptoms of vascular decompensation and liver failure developed within six months. The low prothrombin value (16%), high bilirubin (157/63µmol/L) and symptoms of hepatic encephalopathy (ammonia: 186µmol/L) indicated the progression. Liver transplantation has been performed at her age of 22 years. Ten years passed and the patient is well. WD was diagnosed only after the transplantation by detection of high copper content in the liver and by genetic testing. ATP7B mutations were detected on both alleles (H1069Q/A874V). Her identical twin sister with same mutations was symptomless despite low ceruloplasmin and Kayser-Fleischer ring positivity at her age of 22 years. Liver function tests were negative. She is treated with D-penicillamine. No symptoms or abnormal findings appeared in the last ten years meanwhile she delivered three healthy children. Discussion: Although Wilson's disease is caused by the mutations of ATP7B gene, looking at the fully different clinical presentation in our twins it seems that there is no direct genotype-phenotype correlation. There is no explanation for the differences. Epigenetic and/or environmental factors might play a role. The twins lived in the same family and environment until their age of 19. Thereafter they visited different universities for one semester only. Later they joined again and graduated at the same university. It could be of interest that the first sister had a longer new-born jaundice and underwent medical treatments because of epistaxis repeatedly. Conclusion: The genetic testing is mandatory in siblings of the index patient. The presented two siblings are examples for a totally different manifestation of WD despite the identical gene mutations. The investigation for possible role of both epigenetic and/or environmental factors is in progress.