Alpha-1 antitrypsin deficiency

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at December 30, 2016
StartDiseasesAlpha-1 antitrypsin deficiency

Alpha-1 antitrypsin deficiency (A1AD) is a genetic disorder in which the patient is at an increased risk for diseases of the lung and of the liver, such as early onset emphysema and cirrhosis of the liver. The flexibility and elasticity of lung tissue is hindered, making the development of chronic obstructive pulmonary disease much more likely. Some with this deficiency experience few symptoms or none at all.


Definition & Facts

Alpha-1 antitrypsin, or A1AT, is a protein in the blood that normally is produced by the liver. The function of this protein is to protect tissues, especially that of the lungs, from damaging enzymes. The most common enzyme it protects against is neutrophil elastase, an important enzyme for the destruction of invasive bacteria.

Alpha-1 antitrypsin deficiency results in a deficit of A1AT in the blood. This directly results in an inability for the patient's body to reduce neutrophil elastase. When left unchecked, an excess of neutrophil elastase will break down the elastin that contributes to the lungs' elasticity. This reduction of elasticity leads to many disorders related to the lung, chief among them being emphysema/chronic bronchitis, otherwise known as chronic obstructive pulmonary disease (COPD).

Because A1AD is a condition in which the liver is unable to produce A1AT, there may be other abnormalities in the liver as well, such as an increase in scar tissue that causes cirrhosis.

Symptoms & Complaints

The symptoms of alpha-1 antitrypsin deficiency primarily concern the lungs and the liver. With this condition, airflow in the lungs is reduced, causing shortness of breath. There may be a reduction in oxygen in the blood.

A wet cough and increased production of mucus are other symptoms of COPD. Asthma, another symptom of A1AD, has similar symptoms to COPD, such as decreased airflow, coughing, and mucus production, but is more episodic.

Occurrence of pneumothorax is much more likely, in which the lung detaches from the chest wall, causing sharp pain and shortness of breath. While small instances of spontaneous pneumothorax are not uncommon and in healthy individuals will typically resolve themselves, more severe cases of pneumothorax require medical attention.

Damage to the liver is also common with A1AD, due to a buildup of abnormal A1AT within the organ. Cirrhosis is a disease in which normal liver tissues is gradually replaced by scar tissue, reducing its functioning. This can occur due to the constant, pervasive damage caused by A1AD. Jaundice, a yellow pigmentation to the skin and whites of the eyes (sclera) that is caused by liver damage and associated diseases, might also be a result.

Alpha-1 antitrypsin deficiency increases the risk of various cancers including lung cancer, liver cancer, gallbladder cancer, and lymphoma.


Alpha-1 antitrypsin deficiency is an inherited disorder caused by mutations in the SERPINA1 gene. Each person has two versions of this gene, which is associated with alpha-1 antitrypsin production, and in the case of A1AD, an individual may have abnormal versions of one or both of these genes.

The two most common abnormal A1AD genes are known as Z and S. Those with two Z genes, or ZZ, are most common. The second most common combination is SZ; these individuals tend to have less symptoms of A1AD than those with ZZ. Many other combinations are possible, since over 70 different abnormal genes have currently been identified. The incidence of A1AD is estimated to occur in up to 1 out of 3,500 people who are ethnically of European descent.

Diagnosis & Tests

Many with alpha-1 antitrypsin deficiency will remain undiagnosed. However, an attempt at diagnosis is usually prompted when a patient presents with one of the many symptomatic diseases, such as COPD or cirrhosis, without identifiable cause or at an age much younger than normal. It is also more likely to be diagnosed if other members of the patient's family are confirmed genetic carriers of A1AD.

A genetic test for the abnormal genes in question is one way to determine the presence of A1AD. The physician may also test the blood to determine if there is a deficit in A1AT in the system.

Treatment & Therapy

Treatment for alpha-1 antitrypsin deficiency tends to revolve around treating the various diseases that are symptomatic of this condition.

In the case of CPOD and related lung diseases, medications that increase airflow work well to improve breathing in the patient, as will oxygen therapy. It is advised that the patient avoid secondhand smoke and quit smoking or never begin in the first place, to reduce the damage to the lungs. Prompt vaccination and treatment of lung diseases as they occur will also help protect the lungs. In the case of greatly damaged lungs, a lung transplant is a possible treatment.

In the case of cirrhosis of the liver, damage is irreversible and thus the patient is encouraged to reduce other sources of damage as much as possible, for example by avoiding the consumption of alcohol. As with the lungs, substantial liver damage may call for a liver transplant.

Those with lung impairment only may be recommended for alpha-1 antitrypsin augmentation therapy. This is a treatment in which the patient receives infusions of A1AT, serving to arrest any further damage to the lungs. Researchers are currently looking into treatments in which the faulty A1AT genes are replaced with normal ones.

Prevention & Prophylaxis

Since A1AD is a genetic disorder, there is no way to prevent it. However, being aware of one's family history can help lead to early diagnosis, reducing the damage that this disorder can do to the lungs and the liver. 

Along with abstaining from smoking and abstaining from alcohol consumption, it is advised that those with A1AD reduce their exposure to other air contaminants such as pollen, dust and fumes, and to things that can damage the liver, such as overconsumption of sugar, medications like paracetamol, and diseases like hepatitis C.