Liver biopsy from an infant with neonatal cholestasis shows periodic acid-Schiff positive, diastase-resistant cytoplasmic globules within periportal hepatocytes. Immunostaining confirms accumulation of a misfolded protein retained in the endoplasmic reticulum. The defective protein is:

• A Alpha-1 antitrypsin (PiZ variant) ✓
• B Ceruloplasmin
• C Transferrin receptor
• D Bile salt export pump

Explanation

Alpha-1 antitrypsin deficiency due to the homozygous PiZZ genotype produces misfolded Z protein that polymerizes and is retained within hepatocyte endoplasmic reticulum, forming PAS positive, diastase resistant globules. This causes neonatal cholestasis and later cirrhosis, independent of the panacinar emphysema seen in the same patients. Bile salt export pump defects cause progressive familial intrahepatic cholestasis, and neither ceruloplasmin nor transferrin forms these inclusions.

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.