Testing for Alpha-1

Updated March 13, 2009

Alpha-1 Antitrysin Deficiency (A1AD) can be detected by a simple blood test that indicates the serum level of alpha-1 antitrypsin (AAT). If the serum blood level is low (usually less than 50% of normal), your physician may order other tests that will determine phenotype and / or genotype. Actually, a number of laboratories automatically have further testing done if the blood concentration is below 50% of normal. Specific tests for the various types of alpha-1 disease are discussed in the sections on liver, lung and skin disease.

There are two different methods of expressing the blood test results for alpha-1 and this can lead to some confusion among patients. Many of the commercially available standards have an abnormally high normal range (1.5 – 3.0 g/L). Expression as a percent of normal is useful, as this is not dependent upon units and can apply to any normal range. The following is a rough approximation of the ranges / levels and how the two systems of interpretation correlate with each other. To convert from the milligrams per decilitre scale to the grams per litre scale, divide by 100.

• Normal average 1.32 grams/litre (g/L) or 25 micro molar (mM).
• Commercial laboratory standards may be inappropriately high (e.g. 1.5-3 g/L) 
• mM = micromolar
• mg/dL = milligrams per decilitre
• g/L = grams per litre 

Most of the PI variants are associated with a normal concentration of AAT. The normal mean concentration is 1.32 g/L, as determined against purified protein. PI MM individuals usually have plasma concentrations of 80-120% of this mean. Expressed on a molar basis, the normal mean is 25 mM. There is considerable overlap in plasma level between PI types. Generally no further PI typing is carried out when the concentration is above 32 micro molar to ensure identifying any non-MM PI types, as in the Table above. (Some laboratories and institutions have slightly different standards for the various cut-off points.)

PI typing is important because a low level of AAT can also occur for non-genetic reasons, such as in respiratory distress syndrome in newborns, conditions of severe protein loss, liver failure, and during the course of cystic fibrosis Measurement of plasma AAT is not always reliable for the identification of heterozygotes. AAT can show a marked increase (up to four-fold) in a wide range of inflammatory conditions, cancer, and liver disease. Pregnancy and estrogen therapy also produce modest increases.