From the Guidelines
Alpha-1 antitrypsin deficiency should be diagnosed and treated promptly to prevent irreversible lung damage and improve quality of life, with the most recent and highest quality study recommending DNA sequencing of the coding regions of the SERPINA1 gene as the gold standard for A1AT deficiency testing 1.
Diagnosis and Treatment
Alpha 1 globulin is a group of proteins found in blood plasma that migrate together during electrophoresis. The most clinically significant protein in this group is alpha-1 antitrypsin (A1AT), which protects lung tissue from damage by neutralizing enzymes released during inflammation. A deficiency in alpha-1 antitrypsin can lead to emphysema and liver disease.
Key Points
- Alpha-1 antitrypsin deficiency is a common genetic disorder that predisposes to chronic obstructive airway disease, chronic liver disease, and rarely to skin and vasculitic disorders 1.
- Testing for A1AT deficiency most commonly involves measuring the serum or plasma A1AT level and targeted genotyping with PCR, but DNA sequencing of the coding regions of the SERPINA1 gene is recommended as the gold standard for A1AT deficiency testing 1.
- Augmentation therapy, which involves regular intravenous infusions of purified A1AT protein, is the treatment of choice for alpha-1 antitrypsin deficiency to maintain protective levels in the lungs.
- Early diagnosis and treatment of alpha-1 antitrypsin deficiency are crucial to prevent irreversible lung damage and improve quality of life, with delayed diagnosis associated with reduced functional status and quality of life 1.
Clinical Implications
The Pi typing nomenclature can only characterize a limited number of different protein phenotypes and may be misleading when different nomenclature is used for the same genetic variant(s), thus adopting the HGVS nomenclature when A1AT deficiency testing is performed using DNA-based methods (genotyping and sequencing) is recommended 1.
Testing and Diagnosis
Testing for alpha 1 globulin abnormalities is done through serum protein electrophoresis, with specific follow-up tests to identify particular protein deficiencies when abnormal patterns are detected. A two-step approach is proposed, where an A1AT ≥ 23mmol/L (≥ 1.2 g/L) rules out severe A1AT deficiency, except for rare variants associated with dysfunctional A1AT, and DNA sequencing is suggested as the initial test in the presence of high clinical suspicion 1.
From the Research
Alpha 1 Globulin Overview
- Alpha 1 globulin is a type of protein found in the blood, which plays a crucial role in various bodily functions.
- Research studies have investigated the relationship between alpha 1 globulin levels and certain diseases, including cardiovascular disease and cancer.
Association with Cardiovascular Disease
- A study published in 1985 2 found that decreased levels of albumin-alpha-1-globulin fraction in serum proteins may be a risk factor for ischemic cardiopathy.
- The study, which followed 7434 middle-aged men over 6.6 years, found a significant inverse relationship between the incidence of myocardial infarction or sudden death and alpha 1 globulin levels.
- The results suggest that low alpha 1 globulin levels, along with other factors such as serum cholesterol, blood pressure, and tobacco use, may be associated with an increased risk of coronary heart disease.
Association with Cancer
- A study published in 1983 3 investigated alpha 1 globulin levels in patients with cancer of the genital tract.
- The study found that 25% of patients had alpha 1 globulin levels below 2% of total plasma protein, and 19% had levels below 1%.
- The results suggest that low alpha 1 globulin levels, particularly due to diminished alpha 1-antitrypsin levels, may be associated with certain types of cancer.