A 9-month-old infant with cholestatic jaundice undergoes liver biopsy. Histology shows periodic acid-Schiff positive, diastase-resistant eosinophilic globules within periportal hepatocytes along with portal fibrosis. Serum alpha-1 antitrypsin level is low. Which phenotype is most likely?

• A PiMM
• B PiMZ
• C PiSS
• D PiZZ ✓

Explanation

The homozygous ZZ phenotype causes misfolding of alpha-1 antitrypsin, which polymerises and accumulates in hepatocyte endoplasmic reticulum, appearing as PAS-positive, diastase-resistant globules in periportal hepatocytes. This drives neonatal cholestasis and childhood cirrhosis, while heterozygous carriers like PiMZ rarely develop significant liver disease. The same misfolded protein is not secreted, causing panacinar emphysema in adults.

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.