What is Alpha-1 Deficiency?

Alpha-1 Antitrypsin Deficiency ("AATD" or "Alpha-1 deficiency") is a genetic condition which can cause serious liver disease in children and liver and/or lung disease in adults. The most common clinical presentation of Alpha-1 Deficiency is lung disease. That is the reason it is also called "Inherited Emphysema" or "Genetic COPD".

Alpha-1 antitrypsin (AAT) is a protein that is produced mostly in the liver. Its primary function is to protect the lungs from neutrophil elastase. Neutrophil elastase is an enzyme that normally serves a useful purpose in lung tissue-it digests damaged or aging cells and bacteria to promote healing. However, if left unchecked, it will also attack healthy lung tissue. Alpha-1 antitrypsin, in sufficient amounts, will trap and destroy neutrophil elastase before it has a chance to begin damaging the delicate lung tissue. Consequently, if an individual doesn't have enough alpha-1 antitrypsin, the enzyme goes unchecked and attacks the lung.

References: Alpha1.org.uk, alpha1.org, alpha1health.com

Alpha-1 Disease

Alpha-1 Lung Disease

People with alpha-1 antitrypsin deficiency are at risk of degeneration of lung function, which may significantly affect quality of life and life expectancy.
Alpha-1 antitrypsin protects the delicate tissues of the lungs by binding to neutrophil elastase, a protein released by white blood cells which digests bacteria and other foreign objects in the lungs. When a person who is deficient of Alpha-1 antitrypsin inhales irritants, or contracts a lung infection, the neutrophil elastase released in the lungs continues digesting irritants unchecked, eventually destroying healthy lung tissue. The eventual result of the destruction of healthy lung tissue by neutrophil elastase is emphysema.

Emphysema is a lung disease caused by the destruction of the delicate walls of small air sacs (alveoli). With this destruction, air sacs lose their elasticity and form larger, inefficient sacs that cannot properly exchange oxygen and carbon dioxide with the bloodstream. In addition, it becomes harder to breathe since each drawn breath inflates the lungs, but the lungs do not return to normal with the exhaled breath. This causes air to become trapped, leading to over-inflation of the air sacs. Emphysema caused by Alpha-1 is a progressive disease-the destructive action continues until the lungs can no longer bring in oxygen to the bloodstream.
However, Alpha-1 Antitrypsin Deficiency emphysema (also known as "genetic" or "inherited" emphysema) is different than emphysema caused by smoking ("acquired" emphysema). In emphysema caused by smoking the damage usually affects the upper portion of the lungs. In the patient with Alpha-1, the lower regions of the lungs are typically first affected. With either cause, the lungs are hyperinflated due to air trapping caused by the destruction of the lung tissue, and the diaphragm is flattened due to the hyperinflation of the lungs.

Alpha-1 Liver Disease

Alpha-1 liver disease can affect infants, children, and adults. It can result in a mild elevation in some liver enzymes that returns to normal in a few weeks or it can lead to liver failure and the need for a liver transplant.
Most Alpha-1 liver research suggests that Alpha-1 liver cell damage is caused by misfolded abnormal alpha-1 antitrypsin protein build up in the part of the cell that manufactures proteins- endoplasmic reticulum. This misfolded protein is unable to move along a pathway leading out of the liver cell and into the blood. Scientists believe that this blockage, combined with other genetic and environmental factors, leads to the liver injury of Alpha-1 patients.

References: Alpha1.org.uk, alpha1.org, alpha1health.com

Clinical presentation

  • Shortness of breath
  • Wheezing or non-responsive asthma
  • Coughing with or without sputum production
  • Recurring respiratory infections
  • Rapid deterioration of lung function
  • Unexplained liver problems and /or elevated liver enzymes 


AAT deficiency results when there is a mutation in the gene that directs the body to make the AAT protein. This gene is located on chromosome 14. Chromosome 14 is not a "sex chromosome," meaning that both males and females have it and can pass it on.

There are many variations or alleles of the AAT gene, but the most common are:

  • M – Normal (associated with normal amounts of AAT protein)
  • S and Z – Abnormal (associated with deficient amounts of AAT protein)
  • Null – Abnormal (deficient; no AAT protein is detected)

Every person has two copies of the AAT gene – one from each parent. It is the combination of genes that an individual receives from the parents that determines whether he or she is "normal," has AAT deficiency, or is a carrier of AAT deficiency.

References: Alpha1.org.uk, alpha1.org, alpha1health.com

How common is Alpha-1 deficiency?

Alpha-1 antitrypsin deficiency is one of the most common genetic disorders worldwide, and its prevalence varies by population. This disorder affects about 1 in 1,500 to 3,500 individuals in European countries and in the US.
Although Alpha-1 is a common genetic disorder, it is often misdiagnosed. Many times patients are told they have asthma, bronchitis, symptoms related to stress, emphysema caused by smoking, or chronic obstructive pulmonary disease (COPD) of unknown cause. It takes an average of three doctors and seven years from the time lung symptoms first appear before proper diagnosis is made.


Although Alpha-1 deficiency is one of the most common genetic disorders in the world, it is often misdiagnosed. Many times patients are told they have asthma, bronchitis, symptoms related to stress, emphysema caused by smoking, or simply chronic obstructive pulmonary disease of unknown cause.

Doctors may suspect Alpha-1 deficiency if:

  • Patient has signs or symptoms of a serious lung condition, especially emphysema, without any obvious cause, at a relative young age (usually less than 45).
  • Patient suffers from lung disease although he/she doesn't have risk factors like smoking and exposure to dust, fumes, and other toxic substances.
  • If patient has a liver disease without any obvious causes
  • If patient have bloodline relatives who have AAT deficiency

The diagnosis of Alpha-1 is usually determined by three tests that require a small sample of blood:

  1. Immunoassay: A simple blood test which determines the amount of AAT protein circulating in the blood.
  2. Phenotyping: Identifies the type of AAT protein present in the blood.
  3. Genotyping: Identifies specific genetic mutations. This is the only test that can detect the null and other rare variations of the AAT gene.

Medical care

At this time, there is no cure for Alpha-1, but there are treatments that can improve symptoms, slow down and sometime even stop progression of the disease:

  • Medications such as bronchodilators or inhaled steroids to help open the airways.
  • Pulmonary rehabilitation to improve breathing.
  • Patients with severe alpha-1 may be candidates for a lung transplant.
  • Augmentation therapy, which may slow down or stop the destruction of lung tissue, may also be prescribed. This treatment increases the level of AAT in the blood.