The periportal red hyaline globules seen here with periodic acid-Schiff (PAS) stain are characteristic for alpha-1-antitrypsin (AAT) deficiency. More persons with AAT deficiency are likely to develop chronic obstructive pulmonary disease with panlobular emphysema. The globules are collections of alpha-1-antitrypsin not being excreted from hepatocytes. This may eventually lead to chronic hepatitis and cirrhosis. Liver disease is more likely to occur in children with AAT deficiency, while lung disease occurs in adults.
The gene for AAT is on chromosome 14. There are over 100 known mutations. The normal allele is designated PiM, and the two most common abnormal alleles are designated PiS and PiZ. Heterozygotes PiMS and PiMZ may on occasion develop pulmonary and/or liver disease, but less often severe. The homozygotes PiSS and PiZZ, and the heterozygote PiSZ, are more likely to develop significant COPD and/or liver disease. The persons most likely to develop severe AAT deficiency and its complications have PiZZ. About 1 in 10 persons of European ancestry has one of the 5 abnormal phenotypes (the normal is PiMM).