Variable Degree of Liver Involvement in Siblings With PiZZ Alpha‐1‐Antitrypsin Deficiency‐related Liver Disease

• Published in: Journal of pediatric gastroenterology and nutrition Vol. 43; no. 1; pp. 136 - 138
• Main Authors: Hinds, R., Hadchouel, A., Shanmugham, N.P., Al‐Hussaini, A., Chambers, S., Cheeseman, P., Mieli‐Vergani, G., Hadžić, N.
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins, Inc 01.07.2006; Lippincott
• Subjects: alpha 1-Antitrypsin Deficiency - blood; alpha 1-Antitrypsin Deficiency - complications; alpha 1-Antitrypsin Deficiency - genetics; alpha 1-Antitrypsin Deficiency - surgery; Aspartate Aminotransferases - blood; Bilirubin - blood; Biological and medical sciences; Biomarkers - blood; Disease Progression; Feeding. Feeding behavior; Female; Fetal Diseases - blood; Fetal Diseases - etiology; Fetal Diseases - genetics; Fetal Diseases - surgery; Follow-Up Studies; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease; Humans; Infant, Newborn; Liver Diseases - blood; Liver Diseases - etiology; Liver Diseases - genetics; Liver Diseases - surgery; Liver Function Tests; Liver Transplantation; Male; Phenotype; Platelet Count; Retrospective Studies; Serum Albumin - metabolism; Severity of Illness Index; Siblings; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Digestive diseases; Hepatic disease; Metabolic diseases; α1-Antitrypsine deficiency; Sibling; Gastroenterology
• ISSN: 0277-2116; 1536-4801
• DOI: 10.1097/01.mpg.0000226370.09085.39

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.