Alpha-1 antitrypsin deficiency

From WikiMD's Wellnesspedia

Other Names: AAT deficiency; A1AT deficiency; AATD; Alpha 1 antitrypsin deficiency

Alpha-1 antitrypsin deficiency (AATD) is an inherited disease that 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.

Alpha-1 antitrypsin deficiency.PAS Diastase.jpg
Conditions associated with Alpha-1 Antitrypsin Deficiency.png


Cause[edit | edit source]

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.

Inheritance[edit | edit source]

It is inherited in a codominant manner. AAT deficiency is an inherited disease. “Inherited” means it is passed from parents to children through genes. Every person inherits two AAT genes, one gene from each parent. If you inherit a mutated gene from each parent, you will have AAT deficiency.

If you inherit a mutated AAT gene from one parent and a normal AAT gene from the other parent, you are a carrier for the condition. You might have lower levels of AAT protein in your blood, but you most likely will not have AAT deficiency. However, you might develop some complications of AAT deficiency if you smoke or regularly breathe in dust and fumes. You might also pass the mutated gene to your children.

The AAT gene can have different mutations. The most common mutations that cause AAT deficiency are called PiZ and PiS.

Riskfactors[edit | edit source]

  • AAT deficiency can affect people of any race or ethnicity. However, the condition occurs most often in white people of European backgrounds.
  • If you have first-degree relatives (siblings, parents, or children) with AAT deficiency, you are at a higher risk for the condition. Even so, it does not mean that you will develop one of the diseases related to the condition.
  • Some risk factors make it more likely that you will develop lung disease if you have AAT deficiency. Cigarette smoking is the leading risk factor for serious lung disease if you have AAT deficiency. Your risk for lung disease also may go up if you breathe in dust, fumes, or other toxic substances.

Signs and symptoms[edit | edit source]

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.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

30%-79% of people have these symptoms

  • Hepatitis(Liver inflammation)
  • [[Hepatomegaly](Enlarged liver)
  • Jaundice(Yellow skin)

5%-29% of people have these symptoms

  • Cirrhosis(Scar tissue replaces healthy tissue in the liver)
  • Nephrotic syndrome

1%-4% of people have these symptoms

Diagnosis[edit | edit source]

Alpha 1-antitrypsine deficiency lung CT scan.JPEG
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AAT deficiency usually is diagnosed after you develop a lung or liver disease that is related to the condition. But knowing the symptoms and getting an early diagnosis is important to help prevent serious disease, especially with treatment and lifestyle changes.

Diagnostic tests Your doctor may recommend tests to confirm a diagnosis of AAT deficiency. He or she also may recommend tests to check for lung- or liver-related conditions.

  • A blood test can check the level of AAT protein in your blood. If the level is lower than normal, it is likely that you have AAT deficiency.
  • A genetic test is the most certain way to check for AAT deficiency and should be done to confirm the results of the blood test and find the mutation in the AAT gene. A genetic counselor can help you understand what to expect from a genetic test and what your results mean.

Lung tests

  • If you have a lung disease related to AAT deficiency, your doctor may recommend pulmonary (lung) function tests and imaging tests such as a chest CT scan.
  • Lung function tests measure how much air you can breathe in and out, how fast you can breathe air out, and how well your lungs deliver oxygen to your blood. CT scans use X-rays to create detailed pictures of parts of the body.
  • These tests show how well your lungs are working and whether you have COPD or other lung diseases.

Treatment[edit | edit source]

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 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).

NIH genetic and rare disease info[edit source]

Alpha-1 antitrypsin deficiency is a rare disease.


Alpha-1 antitrypsin deficiency Resources

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