State-of-the-art testing for alpha-1 antitrypsin deficiency

Alpha-1 antitrypsin deficiency (AATD) is a genetic condition characterized by low serum levels of the protein alpha-1 antitrypsin. Because there are no unique clinical symptoms that point to a definitive diagnosis of AATD, laboratory testing is crucial to differentiate this disease from others.

To summarize advances in laboratory techniques used to test for AATD.

Data were sourced from a nonsystematic literature review of MEDLINE and the author's personal literature collection, and by checking reference lists of sourced articles.

Since the original description of AATD by Laurell and Eriksson in 1963, testing methods have undergone major changes. Currently, alpha-1 antitrypsin protein is quantified by immunologic measurement in serum, and the phenotype is characterized by isoelectric focusing and/or targeted genotyping of predefined mutations. In addition, whole-gene sequencing of the gene SERPINA1 can be undertaken. However, this is costly and generally used only if targeted genotyping cannot conclusively identify the variant. The introduction of next-generation sequencing (NGS), which enables rapid and accurate sequencing of large quantities of DNA fragments in a single reaction, may help reduce costs. With its increasing availability, NGS may begin to appear in testing protocols. Clinical guidelines recommend that patients are tested for AATD if they have chronic irreversible airflow obstruction, especially those with early onset disease or a positive family history of AATD. Despite this, AATD is still underrecognized, and significant delays exist between symptom onset and diagnosis.

Traditional testing practices have limitations. Screening programs that incorporate NGS are the most comprehensive methods available for accurate diagnosis of AATD.