Alpha 1 Antitrypsin Deficiency: Your Body's Hidden Threat

Alpha 1 Antitrypsin (A1AT) is a vital protein produced primarily by the liver that protects your lungs from damage. When there's a deficiency, it can lead to serious respiratory and liver conditions that may go undetected until significant damage has occurred.

What Is Alpha 1 Antitrypsin?

Alpha 1 Antitrypsin (A1AT) is a protective protein made mainly by the liver. Its primary function is to shield the lungs from neutrophil elastase, an enzyme that helps fight infections but can damage lung tissue if left unchecked. In healthy individuals, A1AT acts as a bodyguard for your lungs, neutralizing this potentially harmful enzyme before it can cause damage.

The protein is encoded by the SERPINA1 gene, and when mutations occur in this gene, it can lead to Alpha 1 Antitrypsin Deficiency (AATD). This genetic condition results in abnormally low levels of A1AT in the bloodstream. Without sufficient A1AT protection, neutrophil elastase runs rampant, gradually breaking down the elastic fibers that allow your lungs to expand and contract during breathing.

How Alpha 1 Antitrypsin Deficiency Affects Your Body

When A1AT levels are insufficient, two major organ systems bear the brunt of the damage: the respiratory system and the liver. In the lungs, unchecked neutrophil elastase destroys the elastic tissue, particularly in the lower lobes. This destruction leads to emphysema, a condition characterized by shortness of breath, chronic cough, and wheezing—often misdiagnosed as asthma or smoking-related COPD.

Liver complications arise from a different mechanism. Mutated A1AT proteins can't be properly secreted from liver cells, causing them to accumulate within the liver. This buildup can lead to liver damage, cirrhosis, and in severe cases, liver failure. Interestingly, not everyone with AATD develops both lung and liver problems; some may experience predominantly respiratory symptoms, while others face more severe liver complications.

The severity of symptoms varies widely depending on which genetic variants a person carries. The most common problematic variant is the Z allele, with individuals carrying two Z alleles (ZZ) typically experiencing the most severe deficiency and symptoms.

Treatment Options Comparison

Several treatment approaches exist for managing Alpha 1 Antitrypsin Deficiency, with options varying based on symptom severity and affected organs. Augmentation therapy, which replaces the missing protein, represents the only specific treatment for lung disease associated with AATD.

Below is a comparison of the main treatment providers and approaches:

Provider	Treatment Type	Administration	Frequency
Grifols	Prolastin-C (A1AT augmentation)	Intravenous	Weekly
CSL Behring	Zemaira (A1AT augmentation)	Intravenous	Weekly
Takeda	Aralast NP (A1AT augmentation)	Intravenous	Weekly
GlaxoSmithKline	Respiratory symptom management	Inhalers/Oral	Daily

Beyond augmentation therapy, symptom management is crucial. This includes bronchodilators for breathing difficulties, pulmonary rehabilitation programs, and in severe cases, oxygen therapy. For those with liver involvement, monitoring liver function becomes essential, with liver transplantation being an option for end-stage liver disease.

The Alpha-1 Foundation provides resources and support for patients navigating these treatment options, emphasizing the importance of personalized care plans developed with healthcare specialists.

Benefits and Limitations of Current Approaches

Augmentation therapy has shown significant benefits in slowing the progression of emphysema in individuals with AATD. Studies have demonstrated that regular infusions can maintain A1AT levels above the protective threshold, reducing the rate of lung density loss. Patients often report improved quality of life and fewer respiratory exacerbations when consistently receiving this therapy.

However, several limitations exist with current treatment approaches. Augmentation therapy is expensive, with annual costs potentially exceeding $100,000 depending on the product and dosing regimen. Additionally, this therapy addresses only the lung manifestations of AATD, offering no benefit for liver disease. The intravenous administration requires regular healthcare visits, creating potential access barriers for some patients.

Another significant limitation is that augmentation therapy cannot reverse existing lung damage; it can only slow further deterioration. This underscores the critical importance of early detection and intervention. The American Thoracic Society recommends testing for individuals with early-onset emphysema, unexplained liver disease, or a family history of AATD.

Emerging research from Vertex Pharmaceuticals and other biotechnology companies focuses on developing small molecule correctors that could address the protein misfolding in liver cells, potentially benefiting both lung and liver manifestations of the disease.

Testing and Diagnosis Approaches

Diagnosing Alpha 1 Antitrypsin Deficiency involves a multi-step process that begins with simple blood tests and may progress to genetic testing. Unfortunately, AATD remains significantly underdiagnosed, with estimates suggesting less than 10% of affected individuals have been properly identified.

The initial screening typically measures serum A1AT levels. Levels below 57 mg/dL (11 µmol/L) are considered abnormal and warrant further investigation. However, since A1AT is an acute-phase reactant that increases during inflammation, normal or borderline results during infection or inflammation may mask a deficiency.

Phenotyping through isoelectric focusing can identify specific protein variants, while genotyping provides definitive identification of genetic mutations. Companies like Labcorp and Quest Diagnostics offer comprehensive testing panels that include both A1AT levels and genotyping.

The American Lung Association recommends testing for:

Individuals with emphysema, COPD, or asthma that's poorly responsive to treatment
Adults with unexplained liver disease
Individuals with a family history of AATD
First-degree relatives of people with known AATD

Early diagnosis allows for lifestyle modifications that can significantly impact disease progression, particularly avoiding smoking and environmental pollutants that accelerate lung damage.

Conclusion

Alpha 1 Antitrypsin Deficiency represents a significant yet underrecognized genetic condition affecting both respiratory and liver health. Early detection through appropriate testing is crucial, as it allows for timely intervention that can significantly alter disease trajectory. While current treatments like augmentation therapy can effectively slow disease progression, they come with limitations in terms of cost, administration, and inability to reverse existing damage.

For those diagnosed with AATD, a comprehensive management approach involving specialists in pulmonology, hepatology, and genetics offers the best outcomes. Organizations like the Alpha-1 Foundation provide valuable resources and community support. As research continues to advance, particularly in the areas of gene therapy and small molecule correctors, the future holds promise for more effective and convenient treatment options that may address both the lung and liver manifestations of this condition.

Citations

This content was written by AI and reviewed by a human for quality and compliance.