Alpha-1 antitrypsin deficiency results from a mutation in a gene called SERPINA1. This mutation causes the body to make reduced levels or an abnormal form of a protein called alpha-1 antritrypsin.
Alpha-1 antitrypsin normally protects the body from a powerful enzyme made by white blood cells called neutrophil elastase. The normal function of neutrophil elastase is to fight infections. However, in patients with alpha-1 antitrypsin deficiency, neutrophil elastase is not properly controlled and it can damage the lungs.
If abnormal alpha-1 antitrypsin protein is made by the body as a result of a mutation, it may accumulate in the liver, causing liver disease.
Alpha-1 antitrypsin deficiency may be difficult to diagnose, because no single physical sign or symptom can be used to confirm a diagnosis. Genetic testing and blood tests may provide a more conclusive diagnosis.
Clinical exam: A clinical examination of the respiratory system and chest, either with X-rays or by listening for abnormal sounds with a stethoscope, may help identify respiratory abnormalities in patients. Checking for the various respiratory symptoms associated with the disease can help in making a diagnosis. Physicians can also look for signs of increased respiratory work or airflow obstruction.
Genetic tests: Mutations in the SERPINA1 gene are known to cause alpha-1 antitrypsin deficiency. Genetic tests can be used to check for these mutations and diagnose alpha-1 antitrypsin deficiency.
Blood tests: Tests can be performed to measure the level of alpha-1 antitrypsin in a patient's blood. Low levels may indicate that the patient is affected with alpha-1 antitrypsin deficiency.
signs and symptoms
Respiratory problems: Individuals with alpha-1 antitrypsin deficiency usually experience respiratory symptoms, including shortness of breath following mild activity, reduced ability to exercise, coughing, wheezing, recurring respiratory infections, fatigue, and rapid heartbeat upon standing. Patients may also spit up mucus from the respiratory tract.
Liver problems: About 10% to 15% of patients with alpha-1 antitrypsin deficiency develop liver disease, with symptoms including a swollen abdomen, swollen feet or legs, and yellowing of the skin and whites of the eyes. Scarring of the liver, called cirrhosis, may also occur.
Panniculitis: A small number of patients with alpha-1 antitrypsin deficiency may develop panniculitis, a condition in which the skin becomes hardened and painful lumps and patches appear.
Emphysema: Patients may develop emphysema, a condition in which the small air sacs in the lungs (called alveoli) become damaged. Patients with emphysema experience difficulty breathing, a hacking cough, and a barrel shaped chest.
Airway problems: Alpha-1 antitrypsin deficiency may lead to a number of other respiratory problems, including chronic bronchitis (an inflammation of the airways of the lungs) and bronchiectasis (an irreversible dilation of some airways in the lungs). Infection of the upper respiratory tract may be observed in some patients.
Emphysema and cirrhosis of the liver are both life-threatening conditions and may contribute to death in patients with alpha-1 antitrypsin deficiency. However, not all patients with alpha-1 antitrypsin deficiency develop these severe complications.
Alpha-1 antitrypsin normally protects the body from a powerful enzyme made by white blood cells, called neutrophil elastase. The normal function of neutrophil elastase is to fight infections. However, in patients with alpha-1 antitrypsin deficiency, neutrophil elastase is not properly controlled and it can damage the lungs.
Liver disease: If abnormal alpha-1 antitrypsin protein is made by the body as a result of a mutation, it may accumulate in the liver, causing liver disease.
Alpha-1 antitrypsin deficiency is known to result from inheriting a mutated form of the SERPINA1 gene. SERPINA1 makes a protein that normally protects the body from a powerful enzyme made by white blood cells called neutrophil elastase. Individuals normally have two copies of the SERPINA1 gene. An individual with just one mutated copy of SERPINA1 has a low likelihood of developing alpha-1 antitrypsin deficiency, but an individual carrying two mutated copies of SERPINA1 is likely to develop the disease. Therefore, couples in which each parent has a mutated SERPINA1 gene are at a greater risk of having a child affected with alpha-1 antitrypsin deficiency, as each parent could pass a mutated copy of SERPINA1 to the child.
Some mutations in the SERPINA1 gene are not as severe as others and only slightly reduce the ability of the gene to function properly. Individuals carrying these less severe mutated forms of SERPINA1 have a lower risk of passing the disease to children.