What is Alpha-1 Antitrypsin (A1AT) deficiency?

From the Guidelines

Alpha-1 antitrypsin deficiency is a genetic disorder characterized by an insufficient amount of serum alpha-1 antitrypsin, a plasma protein with antiproteolytic activity, which predisposes individuals to chronic obstructive airway disease, chronic liver disease, and other disorders. This condition is defined by a lack of alpha-1 antitrypsin (AAT), a protein that protects the lungs and liver from damage. According to the American Thoracic Society and European Respiratory Society statement 1, AAT deficiency is a common genetic disorder that can lead to chronic obstructive airway disease, chronic liver disease, and rarely to skin and vasculitic disorders.

The primary effects of AAT deficiency are on the lungs, causing emphysema, especially in the lower lungs, and chronic obstructive pulmonary disease (COPD), particularly in people who smoke. It can also affect the liver, leading to cirrhosis and liver failure in some patients. The deficiency occurs due to mutations in the SERPINA1 gene, with the most common problematic variant being the Z allele. People with two Z alleles (ZZ) typically have the most severe deficiency.

Treatment and Management

Treatment for AAT deficiency includes augmentation therapy with intravenous AAT for those with emphysema, which helps slow lung damage by replacing the missing protein. Augmentation therapy in moderately advanced emphysema due to severe alpha-1 antitrypsin deficiency can reduce mortality and slow disease progress 1. Other treatments include standard COPD therapies like bronchodilators, corticosteroids, and oxygen therapy. Patients should avoid smoking, get vaccinations against respiratory infections, and may need liver monitoring. In severe cases, lung or liver transplantation might be necessary.

Key Considerations

• Early diagnosis is crucial, especially in family members of affected individuals, as lifestyle modifications can significantly impact disease progression.
• Genetic testing for AAT deficiency is important for identifying asymptomatic individuals at high risk of having AAT deficiency, allowing them to lead healthier lifestyles that may prevent or delay the onset of disease 1.
• Patients with AAT deficiency should be managed by a multidisciplinary team, including pulmonologists, hepatologists, and other healthcare professionals, to ensure comprehensive care.

From the FDA Drug Label

GLASSIA is an Alpha1-Proteinase Inhibitor (Human), indicated for chronic augmentation and maintenance therapy in individuals with clinically evident emphysema due to severe hereditary deficiency of Alpha1-PI, also known as alpha1-antitrypsin (AAT) deficiency

• Alpha-1 Antitrypsin (A1AT) deficiency is a severe hereditary deficiency of Alpha1-PI, also known as alpha1-antitrypsin (AAT) deficiency, which can cause clinically evident emphysema 2
• It is characterized by a lack of the alpha1-antitrypsin protein, which can lead to lung disease 2
• The exact definition and description of Alpha-1 Antitrypsin (A1AT) deficiency can be found in medical literature, such as the WHO memorandum and other clinical references 2

From the Research

Definition and Prevalence of Alpha-1 Antitrypsin (A1AT) Deficiency

• Alpha-1 Antitrypsin Deficiency (AATD) is a genetic disorder characterized by low serum levels of AAT, the main protease inhibitor in human serum 3.
• The prevalence of AATD in Western Europe and the USA is estimated at approximately 1 in 2,500 and 1 in 5,000 newborns, respectively, with a higher prevalence in populations of Scandinavian descent 3.
• AATD is caused by mutations in the SERPINA1 gene encoding AAT and is inherited as an autosomal recessive trait 3, 4.

Clinical Manifestations of AATD

• The clinical manifestations of AATD may vary widely between patients, ranging from asymptomatic to fatal liver or lung disease 3.
• Common clinical manifestations include pulmonary emphysema, liver cirrhosis, and rare cases of necrotizing panniculitis and secondary vasculitis 3, 5.
• Type ZZ and SZ AATD are risk factors for the development of respiratory symptoms, early onset emphysema, and airflow obstruction early in adult life 3.
• Environmental factors such as cigarette smoking and dust exposure are additional risk factors that can accelerate the progression of AATD 3, 4.

Diagnosis and Treatment of AATD

• Diagnosis of AATD can be established by detection of low serum levels of AAT and isoelectric focusing 3.
• Treatment for lung disease includes intravenous alpha-1-antitrypsin augmentation therapy, annual flu vaccination, and pneumococcal vaccine every 5 years 3.
• Relief of breathlessness may be obtained with long-acting bronchodilators and inhaled corticosteroids, while end-stage liver and lung disease can be treated by organ transplantation 3, 6.
• Individualized pulmonary rehabilitation, exercise, and educational programs can also improve patient quality of life and encourage health-enhancing behavior 6.