AAT deficiency (AATD) is caused by mutations in the SERPINA1 gene, and can lead to COPD, liver, and skin disease. The most common mutation is Z (Glu342Lys, rs28929474) but more than 200 pathological variants exist. In Ireland 1 in 25 people are heterozygous for the Z variant. Globally, AATD is under-diagnosed and prolonged delays in diagnosis are common. Joint ATS/ERS guidelines advocate screening all COPD, refractory asthma, cryptogenic liver disease and panniculitis patients, as well as first degree relatives of known AATD patients.

23,000 individuals have been screened following ATS/ERS guidelines in the Irish national targeted detection programme. AAT levels are determined by immune turbidimetry and AAT phenotyping is by isoelectric focusing with immunofixation. Rare mutations are identified by sequencing of the SERPINA1 gene. Allied to this activity, Alpha-1 Foundation Ireland maintains an education and outreach programme to raise awareness of AATD and encourage increased testing.

We have identified 442 ZZ, 487 SZ, 142 SS, 4702 MZ, and over 200 individuals with rare clinically relevant phenotypes (e.g. IZ and FZ). Rare and novel SERPINA1 mutations have also been identified, including Mmalton, Mheerlen, Mwurzburg, Smunich, and 6 Null (Q0) mutations.

Our results highlight a high prevalence of AATD and the efficacy of a targeted detection approach. Advantages of a diagnosis include pulmonary and liver surveillance, smoking cessation measures, family member testing, specific treatments, and mitigation against occupational and environmental exposures. Systematic testing for AATD could help reduce the burden of COPD which remains a major cause of morbidity and mortality.