A 40-year-old non-smoker presents with progressive dyspnea and elevated liver enzymes. Liver biopsy shows periodic acid-Schiff (PAS)-positive, diastase-resistant globules within hepatocytes. Serum alpha-1 antitrypsin level is markedly decreased. Which genotype is associated with the most severe liver and lung disease?
- A PiMM
- B PiMZ
- C PiZZ ✓
- D PiSZ
Correct answer: C. PiZZ
Explanation
Alpha-1 antitrypsin deficiency is caused by mutations in the SERPINA1 gene. The PiZZ genotype produces the most severe deficiency (serum levels approximately 10-15% of normal) and causes both liver disease (due to accumulation of misfolded protein in hepatocytes) and early-onset panacinar emphysema. PiMM is normal; PiMZ and PiSZ are carriers with intermediate risk.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.