A 40-year-old non-smoker presents with progressive dyspnea and exertional breathlessness. Chest X-ray shows lower zone hyperinflation. Liver examination reveals firm hepatomegaly. Serum alpha-1 antitrypsin level is markedly reduced. Liver biopsy shows PAS-positive, diastase-resistant globules in periportal hepatocytes. What is the inheritance pattern of this condition?
- A Autosomal recessive ✓
- B Autosomal dominant
- C X-linked recessive
- D Mitochondrial inheritance
Correct answer: A. Autosomal recessive
Explanation
Alpha-1 antitrypsin deficiency is an autosomal recessive disorder caused by mutations in the SERPINA1 gene on chromosome 14. The Z allele causes polymerization and accumulation of misfolded protein in hepatocyte endoplasmic reticulum, producing PAS-positive, diastase-resistant globules. The PiZZ genotype causes both liver disease (cirrhosis) and panacinar emphysema due to lack of protection against neutrophil elastase. Only homozygous or compound heterozygous states cause disease.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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