title: Wilson disease in septuagenarian siblings: Raising the bar for diagnosis.
abstract: Wilson Disease (WD) usually presents in the first decades of life, although rare patients have a later presentation. We report the clinical 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 mug/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 clinical 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.
authors.affiliation: Division of Liver Diseases, Recanati/Miller Transplant Institute, The Mount Sinai Medical Center, New York, NY, USA.
authors.forename: Aftab
authors.initials: A
authors.lastname: Ala
authors.forename: Jimo
authors.initials: J
authors.lastname: Borjigin
authors.forename: Arnold
authors.initials: A
authors.lastname: Rochwarger
authors.forename: Michael
authors.initials: M
authors.lastname: Schilsky
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000368:Aged; D027682:Cation Transport Proteins / Q000235:genetics; D000073840:Copper-Transporting ATPases; D005260:Female; D006527:Hepatolenticular Degeneration / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D006801:Humans; D008297:Male; D009154:Mutation; D035781:Siblings
chemical_list: D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases