A 35-year-old man presents with progressive dyspnea and deranged liver function tests. Liver biopsy shows eosinophilic PAS-positive, diastase-resistant globules within the cytoplasm of periportal hepatocytes. Serum protein electrophoresis shows a deficient alpha-1 band. The underlying defect involves:
- A Accumulation of misfolded alpha-1 antitrypsin within hepatocyte endoplasmic reticulum ✓
- B Impaired excretion of copper into bile due to ATP7B mutation
- C Defective apolipoprotein B secretion causing triglyceride retention
- D Iron deposition within lysosomes due to hepcidin deficiency
Explanation
In the PiZZ genotype of alpha-1 antitrypsin deficiency, a single amino acid substitution causes the mutant Z protein to polymerize and be retained within the hepatocyte endoplasmic reticulum rather than secreted. The retained protein forms the characteristic PAS-positive, diastase-resistant cytoplasmic globules, predominantly in periportal hepatocytes. Low circulating enzyme levels cause panacinar emphysema, while the retained protein causes toxic hepatocellular injury. ATP7A relates to Wilson disease, apoB defects cause abetalipoproteinemia, and hepcidin defects cause hemochromatosis.
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.