Wilson disease in septuagenarian siblings: Raising the bar for diagnosis

Authors

  • Aftab Ala,

    1. Division of Liver Diseases, Recanati/Miller Transplant Institute, The Mount Sinai Medical Center, New York, NY
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  • Jimo Borjigin,

    1. Department of Physiology, University of Michigan Medical School, Ann Arbor, MI
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  • Arnold Rochwarger,

    1. Division of Gastroenterology and Hepatology, New York Weill Cornell Medical Center, New York, NY
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  • Michael Schilsky

    Corresponding author
    1. Division of Gastroenterology and Hepatology, New York Weill Cornell Medical Center, New York, NY
    2. Center for Liver Disease and Transplantation, New York Weill Cornell Medical Center, New York, NY
    • Associate Professor of Clinical Medicine Medical Director, Center for Liver Disease and Transplantation, New York Weill Cornell Medical Center, 525 E. 68th St. Box #98 M203, New York, NY 10021
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    • fax: 212-746-8134


  • Conflict of interest: Nothing to report.

Abstract

Wilson Disease (WD) usually presents in the first decades of life, although rare patients have a later presentation. We report the clincial features, diagnostic evaluation, and outcome with treatment of two septuagenarian siblings evaluated as part of a research trial for treatment of neurological WD. The index case was a 72-year-old woman who suffered progressive neurological disability, then developed sub-fulminant liver failure. Her sibling was a 70-year-old man with minimal neurological symptoms and a mild depressive disorder. His liver biopsy revealed only steatosis and minimal fibrosis and an elevated hepatic copper content (671 μg/g dry weight liver). Molecular studies demonstrated compound heterozygosity for disease specific ATP7B mutations E1064A and H1069Q in both patients. Both individuals were treated with trientine and Zn followed by Zn maintenance therapy. Over the last 5 years, the clincial course stabilized and improved, although the index case recently died from bronchopneumonia. In conclusion, advanced age and different clinical presentations of these two subjects with identical ATP7B mutations raises the question of the degree of penetrance for these and other ATP7B mutations. Environmental and extragenic factors are pivotal determinants of disease phenotype. We suggest that WD must be considered at all ages in patients with hepatic disease, neurological disease, or psychiatric symptoms. (HEPATOLOGY 2005;41:668–670.)

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