title: Variable degree of liver involvement in siblings with PiZZ alpha-1-antitrypsin deficiency-related liver disease.
abstract: PiZZ alpha-1-antitrypsin deficiency is the commonest genetic cause of chronic liver disease, but only 10-15% of PiZZ individuals develop liver disease in childhood. Studies have demonstrated varying patterns of disease progression within siblings with the PiZZ phenotype. We retrospectively analysed the case-notes of all patients diagnosed with PiZZ A1ATD between 1978-2002 and compared the pattern of liver disease between affected siblings. We identified 29 families with more than 1 child with the PiZZ phenotype. Twenty-one (72%) PiZZ siblings of the 29 probands had liver disease, which was concordant for severity in 6 (29%), while 8 (28%) had no liver involvement. Five of 7 children requiring liver transplantation had siblings with no persistent liver dysfunction. This study suggests that there is a variable degree of liver involvement in siblings with PiZZ A1ATD-related liver disease and environmental and/or other genetic factors must be involved in determining disease severity.
authors.affiliation: Departments of Child Health, King's College London School of Medicine at King's College Hospital, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Hinds
authors.forename: A
authors.initials: A
authors.lastname: Hadchouel
authors.forename: N P
authors.initials: NP
authors.lastname: Shanmugham
authors.forename: A
authors.initials: A
authors.lastname: Al-Hussaini
authors.forename: S
authors.initials: S
authors.lastname: Chambers
authors.forename: P
authors.initials: P
authors.lastname: Cheeseman
authors.forename: G
authors.initials: G
authors.lastname: Mieli-Vergani
authors.forename: N
authors.initials: N
authors.lastname: Hadzić
mesh_terms: D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D005260:Female; D005315:Fetal Diseases / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000601:surgery; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007231:Infant, Newborn; D008107:Liver Diseases / Q000097:blood / Q000209:etiology / Q000235:genetics* / Q000601:surgery; D008111:Liver Function Tests; D016031:Liver Transplantation; D008297:Male; D010641:Phenotype; D010976:Platelet Count; D012189:Retrospective Studies; D012709:Serum Albumin / Q000378:metabolism; D012720:Severity of Illness Index; D035781:Siblings; D019896:alpha 1-Antitrypsin Deficiency / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000601:surgery
chemical_list: D015415:Biomarkers; D012709:Serum Albumin; D001219:Aspartate Aminotransferases; D001663:Bilirubin