AATD is a rare autosomal recessive condition caused by a mutation in the SERPINA1 gene leading to decreased production of the neutrophil-elastase protective protein alpha-1 antitrypsin, thereby increasing the risk of serious lung and liver disease.4,5
Liver disease associated with AAT deficiency (ZZ phenotype) has a variety of clinical presentations, including neonatal cholestasis, chronic hepatitis, cirrhosis or rarely hepatocellular carcinoma.3,6 AATD accounts for around 5 to 10% of cases of neonatal cholestasis. Only a small proportion of ZZ patients (10 to 15%) develop neonatal cholestasis, due to abnormal storage of ZZ AAT within hepatocytes. Around 30% of those neonates develop chronic liver disease. Lung disease appears in adulthood.4-7
Diagnosis
- Absence of the alpha1-globulin peak on serum protein electrophoresis.4
- The gold standard for AATD diagnosis is phenotype analysis of AAT protein by electrophoresis and/or genotype analysis.4,7
3. INSERM. Orphanet. European Union: The portal for rare diseases and orphan drugs. 2021 (accessed 09/2021 at https://www.orpha.net/consor/cgi-bin/Disease.php?lng=EN.)
4. Protocole national de diagnostic et de soins : Déficits de synthèse des acides biliaires primaires. Centre de Référence Coordonnateur de l’Atrésie des Voies Biliaires et des Cholestases Génétiques; 2019.
5. Torres-Durán M, Lopez-Campos JL, Barrecheguren M, et al. Alpha-1 antitrypsin deficiency: outstanding questions and future directions. Orphanet J Rare Dis 2018;13:114.
6. Alpha-1 antitrypsin deficiency. Genetics Home Reference, U.S. National Library of Medicine, 2013. at https://ghr.nlm.nih.gov/condition/alpha-1-antitrypsin-deficiency.)
7. Patel D, Teckman JH. Alpha-1-antitrypsin deficiency liver disease. Clin Liver Dis 2018;22:643-55.
