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Published on: June 9, 2018
Hereditary alpha-1-antitrypsin deficiency and its clinical consequences
1Alpha1 International Registry, c/o Department of Pulmology, Leiden University Medical Center, Leiden, The Netherlands. L.Fregonese@lumc.nl
Orphanet Journal of Rare Diseases
|June 21, 2008
Summary
Alpha-1-antitrypsin deficiency (AATD) is a genetic disorder causing lung and liver disease due to low alpha-1-antitrypsin (AAT) levels. Diagnosis involves AAT testing, with treatments including augmentation therapy and organ transplantation for severe cases.
Area of Science:
- Genetics and Molecular Biology
- Pulmonology
- Hepatology
Background:
- Alpha-1-antitrypsin deficiency (AATD) is an inherited condition characterized by low serum levels of alpha-1-antitrypsin (AAT), the primary protease inhibitor in human serum.
- It predisposes individuals to pulmonary emphysema, liver cirrhosis, and rarely, panniculitis.
- Prevalence varies, with higher rates in populations of Northern European descent, and is linked to specific genetic alleles like PI Z and PI S.
Purpose of the Study:
- To summarize the genetic basis, clinical manifestations, diagnosis, and management of Alpha-1-antitrypsin deficiency.
- To highlight the risk factors and progression of AATD-related lung and liver diseases.
- To outline current treatment strategies and prognosis for patients with AATD.
Main Methods:
- Review of existing literature on Alpha-1-antitrypsin deficiency.
- Analysis of genetic mutations in the SERPINA1 gene.
- Summary of diagnostic methods including serum AAT levels and isoelectric focusing.
- Compilation of treatment options for pulmonary and hepatic manifestations.
Main Results:
- AATD is caused by SERPINA1 gene mutations, inherited in an autosomal recessive pattern.
- Clinical presentation varies widely, from asymptomatic cases to severe, fatal lung or liver disease.
- ZZ and SZ AATD genotypes are significant risk factors for early-onset emphysema and airflow obstruction.
- Liver disease, including cirrhosis, can occur in childhood or adulthood, with grave prognosis in cirrhotic cases.
Conclusions:
- AATD is a significant genetic risk factor for chronic lung and liver disease.
- Early diagnosis through AAT level testing and genetic analysis is crucial.
- Management involves augmentation therapy for lung disease, supportive care for liver disease, and transplantation for end-stage organ failure.
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