Variable degree of liver involvement in siblings with PiZZ alpha-1-antitrypsin deficiency-related liver disease.
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.
Hinds
R
R
Departments of Child Health, King's College London School of Medicine at King's College Hospital, London, UK.
Hadchouel
A
A
Shanmugham
N P
NP
Al-Hussaini
A
A
Chambers
S
S
Cheeseman
P
P
Mieli-Vergani
G
G
Hadzić
N
N
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
D015415:Biomarkers; D012709:Serum Albumin; D001219:Aspartate Aminotransferases; D001663:Bilirubin