A 47-year-old woman has had worsening dyspnea for the past 5 years. A chest CT scan shows panlobular emphysema. Laboratory studies show the PiZZ genotype of αl-antitrypsin deficiency. A liver biopsy specimen examined microscopically shows abundant PAS-positive globules within periportal hepatocytes. Which of the following molecular mechanisms is most likely responsible for this finding in the hepatocytes?
A.
Excessive hepatic synthesis of αl -antitrypsin
B.
Retention in the endoplasmic reticulum because of poorly folded αl -antitrypsin
C.
Decreased catabolism of αl -antitrypsin in lysosomes
D.
Inability to metabolize αl -antitrypsin
E.
Impaired dissociation of αl -antitrypsin from chaperones