Diagnosis of Alpha-1 Antitrypsin Deficiency

Diagnostic Approach

The American Thoracic Society and the Canadian Thoracic Society recommend testing for alpha-1 antitrypsin (A1AT) deficiency in all patients with COPD, adult-onset asthma with persistent airflow obstruction, and unexplained bronchiectasis 1, 2
The optimal diagnostic approach involves collecting two blood tubes simultaneously: a red-top tube for serum A1AT level measurement and a lavender-top tube for DNA analysis from the buffy coat, as recommended by the American College of Chest Physicians 2
Serum A1AT protein level should never be used as the sole basis for establishing or excluding the diagnosis, according to the American Thoracic Society 7, 5, 6

Isoelectric focusing (IEF) is the gold standard for diagnosis, but DNA sequencing of the SERPINA1 gene is increasingly preferred for definitive diagnosis, as stated by the American Journal of Respiratory and Critical Care Medicine 5, 6
DNA sequencing detects specific mutations in the SERPINA1 gene and provides reliable, definitive results that do not fluctuate, according to the American College of Chest Physicians 2
Phenotyping by IEF can identify most common variants but may miss rare variants, as noted by the American Journal of Respiratory and Critical Care Medicine 7, 5

For suspected A1AT deficiency-associated liver disease, phenotyping plus abdominal ultrasound establishes the diagnosis—liver biopsy is not necessary, as recommended by the American Association for the Study of Liver Diseases 5, 6
Prenatal diagnosis via amniocentesis or chorionic villus sampling uses DNA amplification techniques, according to the American College of Medical Genetics 8

The Canadian Thoracic Society recommends adopting HGVS (Human Genome Variation Society) nomenclature for genetic variants alongside traditional Pi typing during a transition period, to improve accuracy in identifying rare variants and enable better registry data for research 2