Alpha-1-Antitrypsin Level of 249 mg/dL: Interpretation and Management
Direct Answer
An alpha-1-antitrypsin level of 249 mg/dL is within the normal range and does not indicate deficiency in most clinical scenarios, but further evaluation with DNA sequencing of the SERPINA1 gene is warranted if you have high clinical suspicion based on specific risk factors. 1
Understanding the Result
Your A1AT level of 249 mg/dL converts to approximately 1.29 g/L or 23.7 mmol/L, which is above the critical threshold of 120 mg/dL (1.2 g/L or 23 mmol/L) used to rule out severe A1AT deficiency. 1
Normal Reference Ranges
- Normal adult range (M/M phenotype): 100-273 mg/dL 2
- Severe deficiency threshold: <120 mg/dL 1
- Your level of 249 mg/dL falls comfortably within the normal range 2
Critical Caveat: When Normal Levels Don't Rule Out Deficiency
You must proceed to DNA sequencing despite this normal level if ANY of the following high-risk features are present: 1, 3
- Early-onset COPD (before age 40) 1
- Minimal smoking exposure (<10 pack-years) with COPD 1
- Panlobular emphysema (especially basilar predominant) 1, 3
- Family history of COPD or A1AT deficiency 1, 3
- First-degree relative with confirmed A1AT deficiency 1, 4
- History of perinatal jaundice 3
Why Normal Levels Can Be Misleading
A1AT is an acute phase reactant that increases during inflammation, potentially masking underlying deficiency. 5 Patients with true A1AT deficiency can show levels as high as 140 mg/dL (1.4 g/L) during acute illness. 1, 5
Rare dysfunctional variants (like Pi*F) produce normal circulating A1AT levels that are non-functional, making serum measurement alone inadequate for diagnosis. 1, 3
Recommended Next Steps
If You Have High-Risk Features:
Proceed directly to DNA sequencing of SERPINA1 gene (exons 2-5) regardless of your normal A1AT level. 1, 3 This is the gold standard test that detects all >300 genetic variants in a single assay. 3
If You Have Moderate-Risk Features Only:
Moderate-risk features include: 3
- COPD without high-risk features
- Unexplained bronchiectasis
- Adult-onset asthma with persistent airflow obstruction
- Liver cirrhosis
- ANCA-positive vasculitis
For moderate-risk patients with your level of 249 mg/dL, no further testing is needed at this time unless clinical suspicion remains high. 1
If You Are a First-Degree Relative of Someone with A1AT Deficiency:
You should undergo genetic testing regardless of your normal serum level to determine your carrier status and disease risk. 1, 4 Siblings and offspring of heterozygous individuals have a 25% chance of being heterozygous themselves. 3
Important Testing Pitfalls to Avoid
Do not test during acute illness, active infection, recent surgery, or inflammatory conditions, as these artificially elevate A1AT levels and can mask deficiency. 5, 3 If you were tested during such conditions, repeat testing when clinically stable or proceed directly to genetic testing. 5
Do not rely on repeat serum measurements if clinical suspicion remains high – the test-retest reproducibility of A1AT levels is weak due to biological variability. 1 Genetic mutations are invariant, making DNA sequencing more definitive. 4
Clinical Context
Delayed diagnosis of A1AT deficiency is associated with worse overall survival, reduced transplant-free survival, diminished functional status, and lower quality of life due to the irreversible nature of lung damage. 3 The average diagnostic delay is 5.6 years. 6
A1AT deficiency affects an estimated 1 in 3,000-5,000 individuals in North America, making it one of the most common genetic lung disorders, yet the majority of affected individuals remain undiagnosed. 1