alpha 1-antitrypsin deficiency

Alpha 1-antitrypsin deficiency is a hereditary condition that primarily affects the liver and lungs, often manifesting in adulthood. It is caused by changes in the SERPINA1 gene, leading to reduced circulating levels of the protective alpha-1-antitrypsin protein. Individuals with this condition may develop chronic liver disorders such as cirrhosis as well as respiratory problems including emphysema. The condition affects approximately 1 to 5 per 10,000 people, and not all affected individuals experience identical symptoms.

The clinical presentation of alpha 1-antitrypsin deficiency is multi-system in nature. Respiratory symptoms are common and include chronic cough, increased sputum production, hemoptysis, bronchiectasis, and emphysema, while liver involvement can lead to hepatomegaly, cirrhosis, hepatic failure, jaundice, hepatitis, and cholestasis. Additionally, nearly all affected individuals experience splenomegaly and may be at risk for gastric varices. Not all individuals experience every feature, and severity varies widely between patients.

Alpha 1-antitrypsin deficiency is caused by pathogenic variants in the SERPINA1 gene. The SERPINA1 gene produces the alpha-1-antitrypsin protein, which normally helps protect tissues from damage by enzymes such as neutrophil elastase. In individuals with the disorder, mutations in this gene result in reduced functional protein levels, leading to lung tissue damage and liver complications. The condition is inherited in an autosomal recessive pattern, meaning that an affected individual has received one mutated copy from each parent. This pattern implies that siblings of an affected person have a risk of being affected if both parents are carriers, and genetic counseling is recommended for families considering future pregnancies.

Currently, management of alpha 1-antitrypsin deficiency focuses on supportive care and symptom management as no treatments have been specifically approved for this condition. Care typically involves a multidisciplinary team and regular surveillance to monitor respiratory and liver function, enabling early detection of complications. This ongoing surveillance is an essential part of long-term care, and patients are encouraged to maintain regular follow-up with healthcare providers and specialists. Genetic counseling is also recommended to help families understand inheritance and treatment options, and individuals should discuss all available management strategies with their care team.

The course of alpha 1-antitrypsin deficiency is highly variable, with outcomes ranging from stable long-term health to progressive liver and lung complications. With current standards of care, many individuals manage their symptoms into adulthood, although the condition may progress in some patients over time. Outcomes described in medical literature continue to evolve as standards of care improve. Given the variability in clinical presentation, families are encouraged to consult with specialists and genetic counselors for personalized guidance and to consider support networks as part of ongoing care.

Alpha 1-antitrypsin deficiency remains an active area of research with numerous ongoing clinical trials investigating new treatment approaches. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility for participation.