title: Concordance rates of Wilson's disease phenotype among siblings.
abstract: Wilson's disease (WD) is an autosomal recessive disorder characterized by the functional disruption of adenosine triphosphatase 7B (ATP7B), which results in positive copper balance. Although the primary manifestations of the disease are hepatic or neurological in scope, the factors that cause a very diverse picture of WD are not well researched. We compared the first clinical presentation, ages of onset and diagnosis, copper metabolism parameters, and ceruloplasmin levels between index cases (ICs) and their siblings. We examined 73 ICs and 95 siblings from 73 families, including a total of 168 patients with biochemical and genetically confirmed WD diagnoses. We observed an 86% concordance rate of primary clinical symptoms among ICs with hepatic symptoms and their siblings. There was 66% concordance among ICs with neurological symptoms and their siblings. No differences regarding age at onset of symptoms or copper metabolism parameters at diagnosis were identified between hepatic ICs and their siblings. The age at symptom onset did not differ between neurological ICs and their siblings, although ICs presented lower ceruloplasmin and serum copper levels. These results demonstrate a high intra-familial concordance of the clinical and biochemical presentation of WD, suggesting that similar factors shared within the same families strongly influence the disease presentation.
authors.affiliation: 2nd Department of Neurology, Institute of Psychiatry and Neurology, 9 Sobieskiego Str., 02-957, Warsaw, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Chabik
authors.forename: Tomasz
authors.initials: T
authors.lastname: Litwin
authors.forename: Anna
authors.initials: A
authors.lastname: Członkowska
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D027682:Cation Transport Proteins / Q000235:genetics; D002570:Ceruloplasmin / Q000378:metabolism; D003300:Copper / Q000097:blood / Q000652:urine; D000073840:Copper-Transporting ATPases; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D006527:Hepatolenticular Degeneration / Q000175:diagnosis* / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D009422:Nervous System Diseases / Q000175:diagnosis / Q000235:genetics; D010641:Phenotype; D035781:Siblings; D055815:Young Adult
chemical_list: D027682:Cation Transport Proteins; D003300:Copper; D002570:Ceruloplasmin; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases