Emphysema of early onset associated with a complete deficiency of alpha-1-antitrypsin (null homozygotes).
We have compared lung function in 3 subjects with no alpha 1-antitrypsin (alpha 1-protease inhibitor) (null homozygotes) with subjects having the typical deficiency, PIZZ. We identified a 31-yr-old woman, presenting with severe obstructive lung disease, who had no detectable plasma alpha 1-antitrypsin, indicating homozygosity for a "null" (or PI*QO) allele of alpha 1-antitrypsin. Two of her sisters have a similar deficiency, one with an onset of symptoms at 17 yr of age. Because of the likelihood that there are a number of different PI*QO alleles, the type in this family has been named null Mattawa (QOmattawa). All 3 homozygotes have shown a marked deterioration of lung function over a 7-yr period of follow-up. In contrast, lung function tests of 6 age-matched nonsmoking subjects with alpha 1-antitrypsin deficiency, PI type ZZ, showed no abnormalities of lung function. The 15 to 20% of the normal plasma concentration of alpha 1-antitrypsin associated with the PI*Z allele appears to provide some protection to the lung in comparison with a complete deficiency state.
Cox
D W
DW
Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
Levison
H
H
D000328:Adult; D000483:Alleles; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008099:Liver / Q000503:physiopathology; D008168:Lung / Q000503:physiopathology; D008297:Male; D010375:Pedigree; D010641:Phenotype; D011656:Pulmonary Emphysema / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D000515:alpha 1-Antitrypsin / Q000032:analysis; D019896:alpha 1-Antitrypsin Deficiency
D000515:alpha 1-Antitrypsin