Mode of inheritance: autosomal codominant.- Gene is called SERPINA1 on chromosome 14. - Normal is M (50%)/M (50%); PiMM = 100% function→ S Mutation → 25% function; PiSS = 50% function→ Z Mutation → 10% funtion; PiZZ = 20% function→ 0 mutations → Absent protein

Pathophysiology:- Liver: Impaired secretion of α1-antitrypsin by hepatocytes → intracellular accumulation of α1-antitrypsin → hepatocyte destruction → hepatitis and liver cirrhosis- Lungs: deficiency of α1-antitrypsin in plasma → increased protease activity in the lungs → destruction of the pulmonary architecture → panacinar emphysema

Clinical presentation:- Severe form: Prolonged neonatal jaundice, hepatitis, cirrhosis, and pulmonary emphysema- Mild form: Manifests in adolescence, primarily with pulmonary disease; hepatic symptoms may also be present.- Patients are at increased risk for hepatocellular carcinoma.

Diagnosis: - Electrophoresis (decreased alpha-1 peak), serum antitrypsin level, liver biopsy- Chest x-ray or CT (hyperinflation), pulmonary function tests (obstructive pattern)

Microscopy: Stain with PAS- PAS ⊕ (Periodic acid shiff that stains glycoproteins pink) → stains because stuck in ER- Diastase (destroys glycoproteins) → resistant because cannot reach ER

Therapy: - IV infusion of normal A1AT Protein- Inhalers, supplemental oxygen