A 36-year-old male smoker has 3 years of progressive exertional dyspnea. Spirometry shows airflow obstruction. Chest radiograph reveals striking bibasilar emphysematous bullae with apical sparing, and he has mildly raised transaminases. Serum alpha-1 antitrypsin level is 25 mg/dL (normal 90 to 200 mg/dL). Which phenotype is classically responsible?
- A PiZZ ✓
- B PiMZ
- C PiSS
- D PiMM
Correct answer: A. PiZZ
Explanation
Homozygous PiZZ results from a glutamate to lysine substitution at position 342, causing misfolding and polymerization of alpha-1 antitrypsin inside hepatocytes. This produces very low serum levels, early basal panacinar emphysema accelerated by smoking, and cirrhosis from intrahepatic PAS-positive globules. PiMM is the fully functional normal phenotype, PiMZ gives intermediate levels rarely causing disease, and PiS alone confers only mild reduction insufficient for this presentation.
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.