Alpha-1 antitrypsin deficiency

Genetic disorder with an autosomal inheritance pattern and codominant expression of alleles.

Pulmonary and hepatic manifestations include emphysema, COPD, and cirrhosis.

Granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) and necrotising panniculitis are infrequent complications but can prompt diagnosis.

Plasma AAT levels, protein phenotyping (called Pi-typing), and protein genotyping may be necessary for diagnosis. Rare alleles may require gene sequencing.

Intravenous AAT augmentation therapy benefits some patients.

Alpha-1 antitrypsin (AAT) deficiency is an autosomal codominant genetic disorder (i.e., 1 allele is inherited from each parent and each allele is expressed equally) resulting from AAT allele mutations at the protease inhibitor (PI) locus. PI* allele mutations cause ineffective activity of the specific protease inhibitor alpha-1 antitrypsin, which is the enzyme responsible for neutralising neutrophil elastase and preventing inflammatory tissue damage in the lungs.[1]Laurell CB, Eriksson S. The electrophoretic alpha 1-globulin pattern of serum in alpha 1-antitrypsin deficiency. Scand J Clin Lab Invest. 1963;15:132-140.[2]Brantly M, Nukiwa T, Crystal RG. Molecular basis of alpha 1-antitrypsin deficiency. Am J Med. 1988;84:13-31. http://www.ncbi.nlm.nih.gov/pubmed/3289385?tool=bestpractice.com Variants of the enzyme may also polymerise and accumulate in the liver, resulting in hepatic failure. Alpha-1 antitrypsin is also known as alpha-1 proteinase inhibitor.