Alpha 1 antitrypsin deficiency

Alpha-1 Antitrypsin Deficiency
Synonyms	N/A
Pronounce	N/A
Specialty	N/A
Symptoms	Shortness of breath, wheezing, chronic obstructive pulmonary disease, liver disease
Complications	Emphysema, cirrhosis, liver cancer
Onset	Typically in adulthood
Duration	Chronic
Types	N/A
Causes	Genetic disorder
Risks	Smoking, pollution
Diagnosis	Blood test, genetic testing
Differential diagnosis	N/A
Prevention	N/A
Treatment	Augmentation therapy, liver transplant
Medication	N/A
Prognosis	N/A
Frequency	1 in 2,500 to 1 in 5,000 individuals of European descent
Deaths	N/A

Alpha-1 Antitrypsin Deficiency (AATD) is a genetic disorder that can result in serious lung disease in adults and/or liver disease at any age. It is caused by mutations in the SERPINA1 gene, which encodes the protein alpha-1 antitrypsin (AAT). AAT is primarily produced in the liver and functions to protect the lungs from neutrophil elastase, an enzyme that can degrade connective tissue.

Genetics

Alpha-1 antitrypsin deficiency is inherited in an autosomal codominant pattern. The SERPINA1 gene is located on the long arm of chromosome 14 (14q32.1). The most common alleles are M, S, and Z, with the Z allele being the most significant in terms of disease risk. Individuals with the ZZ genotype have the most severe deficiency of AAT.

Pathophysiology

In individuals with AATD, the liver produces an abnormal form of AAT that cannot be secreted effectively. This leads to low levels of AAT in the blood and lungs, resulting in unchecked activity of neutrophil elastase. The excess elastase activity causes progressive damage to the alveoli, leading to emphysema. In the liver, the accumulation of abnormal AAT can cause hepatocellular damage, leading to cirrhosis and hepatocellular carcinoma.

Clinical Manifestations

Pulmonary

The most common pulmonary manifestation of AATD is chronic obstructive pulmonary disease (COPD), which includes emphysema and chronic bronchitis. Symptoms include dyspnea, chronic cough, and wheezing. The onset of symptoms typically occurs in the third to fourth decade of life, but can be earlier in smokers.

Hepatic

Liver disease in AATD can present as neonatal hepatitis, cirrhosis, or hepatocellular carcinoma. Neonates may present with jaundice, hepatomegaly, and failure to thrive. Adults may develop cirrhosis and its complications, such as portal hypertension and ascites.

Diagnosis

Diagnosis of AATD is confirmed by measuring serum AAT levels and genotyping for the SERPINA1 alleles. A low serum AAT level suggests deficiency, and genotyping can confirm the presence of pathogenic alleles such as Z or S.

Management

Pulmonary

Management of pulmonary disease in AATD includes smoking cessation, bronchodilators, and inhaled corticosteroids. Augmentation therapy with intravenous AAT can slow the progression of lung disease in individuals with severe deficiency.

Hepatic

Liver disease management focuses on monitoring and treating complications of cirrhosis. In cases of end-stage liver disease, liver transplantation may be necessary.

Prognosis

The prognosis of AATD varies depending on the severity of lung and liver involvement. Early diagnosis and management can improve outcomes, particularly with lifestyle modifications such as smoking cessation.

Epidemiology

AATD is most common in individuals of European descent, with an estimated prevalence of 1 in 2,500 to 1 in 5,000. It is less common in other populations.

See also

• Chronic obstructive pulmonary disease
• Cirrhosis
• Genetic disorders

Classification
External resources