Alpha-1 antitrypsin (A1AT) deficiency is an inherited autosomal co-dominant condition that may result in chronic obstructive lung and cirrhotic liver disease. It is caused by specific combinations of mutations in the SERPINA1 gene. The condition affects between 1 in 1500 and 1 in 3500 individuals of European ancestry, is rare in Asian populations and varies between other population ancestry groups. It is usually an adult-onset condition, although the deficiency itself may be detected at birth. Presenting symptoms often include wheezing, shortness of breath and reduced ability to exercise.
An individual’s genetic makeup combines with environmental factors to determine the severity of the condition. Approximately 10% of infants with alpha-1 antitrypsin deficiency will also develop liver disease, as will 15% of adults. Individuals with alpha-1 antitrypsin deficiency are also at higher risk of developing hepatocellular carcinoma.
Several variants of the SERPINA1 exist, each having a different level of functionality. The ‘M’ variant is a fully functioning form, the ‘S’ form is marginally deficient, followed by the ‘Z’ form which is deficient, and a null form which has no activity. Pairs of these various forms, one inherited from each parent, have a combined additive effect in an individual on the overall activity of the alpha-1 antitrypsin. Two null forms is the most severe and two ‘M’ forms is found in unaffected individuals, with other combinations having graded severity.
Testing is indicated in patients who have low serum alpha-1-antitrypsin levels. The Genomic Diagnostics’ test can confirm the diagnosis of A1AT deficiency by detecting the 2 deficiently functioning DNA variants (S and Z) found in the SERPINA-1 gene.