Alpha1-antitrypsin deficiency: An updated review.

Area of Science:

• Genetics
• Pulmonology
• Hepatology

Background:

• Alpha1-antitrypsin deficiency (AATD) is a rare autosomal recessive disorder linked to the SERPINA1 gene's homozygous Z variant.
• It manifests as severe alpha1-antitrypsin deficiency, leading to pulmonary emphysema and/or liver fibrosis.
• Risk factors like smoking, obesity, and alcohol exacerbate AATD's clinical expression.

Purpose of the Study:

• To summarize the clinical manifestations, diagnosis, and management of Alpha1-antitrypsin deficiency.
• To highlight the importance of early detection in patients with COPD and chronic liver disease.
• To discuss current and emerging therapeutic strategies for AATD.

Main Methods:

• Diagnosis relies on serum alpha1-antitrypsin levels, biochemical phenotype determination (isoelectric focusing), or PCR detection of variants.
• SERPINA1 gene sequencing is employed for diagnostic discrepancies.
• A randomized clinical trial informed augmentation therapy guidelines.

Main Results:

• Pulmonary emphysema in AATD is associated with severe deficiency and smoking.
• Liver fibrosis risk increases with obesity and alcohol intake, posing a risk for liver cancer.
• Augmentation therapy is recommended for specific non-smoking adults with confirmed homozygous AATD and emphysema.

Conclusions:

• Early detection of AATD is crucial for carriers of the Z variant, especially in patients with COPD or chronic liver disease.
• While no cure exists for AATD-related liver disease, augmentation therapy offers a treatment option for eligible emphysema patients.
• Future therapies targeting liver alpha1-antitrypsin production may significantly alter AATD patient care.