There are >59 variants which result in varying levels of α1-antitrypsin and are associated with different symptom levels. Phenotypes are designated as Pi phenotypes – M, S, Z, F etc. PIMM (i.e homozygous) have 40% reduction in levels, PiMZ (heterozygous) 85% reduction. One rare type Mduarte produces a normal concentration of functionally deficient protein.
The test should be performed in adults if α1-antitrypsin levels are determined to be below age related median result. Phenotyping should be determined in all children with liver disease irrespective of AAT concentration. Severe genetic deficiencies of α1-antitrypsin (<0.6g/L) occur with an incidence of around 1 in 2,000.
Investigation of genetic origin of α1-antitrypsin deficiency. Used in family screening for deficiency when deficient sibling has been identified. Investigation of all children with liver disease irrespective of α1-antitrypsin levels.
Patients who are homozygous for a deficiency allele or are heterzygous for two deficiency alleles will have a severe reduction of serum α1-antitrypsin (<0.6g/L). A hetererozygous state with one deficiency allele and one “normal” allele will normally have level 0.6-1.4 g/L.
Isoelectric focusing in polyacrylamide gel (pH 4-5).
Sheffield Protein Reference Unit