Alpha 1 Antitrypsin deficiency

It is an inherited condition which predisposes one to the development of COPD and emphysema at an earlier age than one would normally expect. Less commonly it is associated with a predisposition to bronchiectasis and it may also be associated with some forms of liver disease. The condition can be excluded by a simple blood test.

Conditions associated with Alpha-1 Antitrypsin Deficiency

Pathophysiology

Alpha-1 antitrypsin deficiency (AATD) causes an increased risk of having chronic obstructive pulmonary disease (COPD), liver disease, skin problems (panniculitis), and inflammation of the blood vessels (vasculitis). Lung (pulmonary) problems almost always occur in adults, whereas liver and skin problems may occur in adults and children. The age symptoms begin and severity of symptoms can vary depending on how much working alpha-1 antitrypsin protein (AAT) a person has. Symptoms may include shortness of breath and wheezing, repeated infections of the lungs and liver, yellow skin, feeling overly tired (fatigue), rapid heartbeat when standing, vision problems, and weight loss. However, some people with AATD do not have any problems.

Alpha-1 antitrypsin deficiency

Cause

AATD is caused by changes (pathogenic variants, also called mutations) in the SERPINA1 gene and it is inherited in a codominant manner. The genetic changes cause too little or no working alpha-1 antitrypsin protein (AAT) to be made. AAT is made in the liver cells and sent through the bloodstream to the lungs where it helps protect the lungs from damage. Having low levels of AAT (or no AAT) may allow the lungs to become damaged. A build-up of abnormal AAT can cause liver damage. Diagnosis may be suspected by finding low levels of AAT in the blood and confirmed by genetic testing. Treatment may include infusions of AAT. Other treatment depends on the type and severity of the person's medical problems, but may include bronchodilators to open airways, antibiotics for upper respiratory tract infections, and in severe cases, lung transplantation or liver transplantation.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

80%-99% of people have these symptoms

Emphysema Hepatic failure Liver failure

30%-79% of people have these symptoms

Hepatitis Liver inflammation Hepatomegaly Enlarged liver Jaundice Yellow skin

Cause

Alpha-1 antitrypsin deficiency (AATD) is caused by changes (pathogenic variants, also known as mutations) in the SERPINA1 gene. This gene gives the body instructions to make a protein called alpha-1 antitrypsin (AAT). One of the jobs of AAT is to protect the body from another protein called neutrophil elastase. Neutrophil elastase is an enzyme that helps the body fight infections, but it can also attack healthy tissues (especially the lungs), if not controlled by AAT.

Genetic changes that cause AAT may mean that the body's liver cells make too little or no AAT, or make a form (variant) of AAT that does not work well (abnormal AAT). This allows neutrophil elastase to destroy lung tissue, causing lung disease.

In addition, abnormal AAT can build up in the liver and cause damage to the liver, especially in people who have two copies of the specific genetic variant called allele Z (sometimes written as PI*ZZ). Liver problems do not occur in people who do not make any detectable AAT, for example when a person has two null alleles of the SERPINA1 gene.

The severity of AATD may also be worsened by environmental factors such as exposure to tobacco smoke, dust, and chemicals.

Diagnosis

Alpha-1 antitrypsin deficiency (AATD) may first be suspected in people who have symptoms of liver disease at any age, or who have symptoms of lung disease (such as emphysema), especially when there is no obvious cause or it is diagnosed at a younger age.

Confirming the diagnosis involves a blood test showing a low level the alpha-1 antitrypsin protein (AAT) in the blood, and either: Detecting an AAT protein variant that does not work properly (functionally deficient) using a special test called isoelectric focusing. or finding a disease causing change (pathogenic variant, also called mutation) in both copies of the SERPINA1 gene by genetic testing. (This confirms the diagnosis when the above-mentioned tests are not performed or their results are not in agreement.) Specialists involved in the diagnosis may include primary care doctors, lung specialists (pulmonologists), and/or liver specialists (hepatologists ).

Computed tomography of the lung with thin slices (1 mm) showing emphysema and bullae in the lower lung lobes of a subject with type ZZ alpha-1-antitrypsin deficiency. There is also increased lung density in areas with compression of lung tissue by the bullae.

Treatment

In general, the treatment of medical problems associated with alpha-1 antitrypsin deficiency (AATD) includes the standard medical therapies and supportive care for the specific medical problem. However, there is one special therapy available to some people with AATD who have lung problems called augmentation therapy (sometimes called replacement therapy).

Augmentation therapy

Augmentation therapy aims to increase the blood level of alpha-1 antitrypsin protein (AAT) by adding purified, human AAT directly into the person's blood through intravenous (IV) infusion. The goal is to prevent the progression of lung disease. Skin problems usually get better as well. Augmentation therapy does not affect liver disease associated with AATD.

Augmentation therapy is indicated only when people with AATD:

• Are older than 18 years of age.
• Have levels of alpha-1 antitrypsin in blood that are less than 11 micromoles/liter.
• Have pulmonary function tests (spirometer ) that show airway obstruction.
• Do not smoke or have stopped smoking for at least the last 6 months.
• Are willing to be get the infusions weekly at the hospital.
• Do not have immunoglobulin A deficiency, because the therapy with alpha-1 may contain traces of immunoglobulin type A (IgA), and patients with IgA deficiency may have antibodies against IgA.
• In some cases it is also done in people who have normal airflow, but who have a CT scan that shows emphysema in the lung.

Other treatments depend on symptoms but may include:

• Antibiotics to treat infections.
• Bronchodilators and inhaled steroids can help open the airways and make breathing easier.
• Exercise program.
• Oxygen.
• Lung volume reduction surgery.
• Lung transplantation for patients with advanced emphysema due to severe AAT deficiency.
• Liver transplantation for patients with severe liver disease. After a liver transplant the AAT deficiency is corrected, because normal donor liver produces and secretes normal AAT.

Routine recommendations to avoid medical complications include:

• Vaccination against hepatitis A and B.
• Preventive vaccines against influenza and pneumococcal vaccines.
• Avoid using tobacco.
• Avoid or minimize drinking alcohol (for those at risk for liver disease).
• Avoid other environmental risk factors such as chemical exposures.
• Liver function tests periodically for people with two copies of the Z allele (PI*ZZ).
• Lung function test every six to 12 months people with severe AATD.
• Liver ultrasound, in cases of liver disease, every 6 to 12 months to monitor for fibrotic changes (cirrhosis) and liver cancer (hepatocellular carcinoma).

Alpha 1 Antitrypsin deficiency Resources
Need Help Finding a Doctor? WikiMD's DocFinder can help find general and specialist physicians.	Latest articles Most recent articles Ongoing trials.