alpha 1-Antitrypsin deficiency.
alpha 1-Antitrypsin, the major serum protease inhibitor, is a glycoprotein synthesized in the liver. Severe deficiency results in protease-antiprotease imbalance, which predisposes to severe emphysema at a young age. Reduced serum levels reflect inadequate release of alpha 1-antitrypsin by the liver, which may be caused by specific defects in biosynthesis. The deficiency is inherited, with multiple codominant alleles at a single autosomal locus. Homozygous individuals, with severely reduced alpha 1-antitrypsin levels, have dyspnea, pulmonary function abnormalities, and respiratory disability from emphysema, usually in the fifth decade of life, with smokers being affected one decade earlier. Heterozygous individuals have intermediate alpha 1-antitrypsin levels and a more benign clinical course. Heterozygous smokers may have mild pulmonary function abnormalities, but these are of uncertain clinical significance. Hepatic involvement with transient neonatal hepatitis and cirrhosis with subsequent liver failure in adulthood represent the major extrapulmonary manifestations, occurring in 10% of homozygous individuals.
D000328:Adult; D000367:Age Factors; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism; D007231:Infant, Newborn; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008107:Liver Diseases / Q000209:etiology; D008173:Lung Diseases, Obstructive / Q000209:etiology; D010641:Phenotype; D012907:Smoking; D000515:alpha 1-Antitrypsin / Q000096:biosynthesis / Q000235:genetics; D019896:alpha 1-Antitrypsin Deficiency
D000515:alpha 1-Antitrypsin