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What You Need to Know About Alpha-1 Antitrypsin Deficiency

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Your liver is an amazing organ. Your liver cleans your blood of toxins, provides you energy and produces bile for digestion. Another fascinating thing your liver does is to help protect your lungs from infections or inhaled irritants. But an inherited condition can interfere with your liver’s ability to perform this valuable task.

Alpha-1 antitrypsin deficiency (A1ATD) is an inherited condition that causes a severe lack of alpha-1 antitrypsin protein in the blood. That protein’s main function is to work together with cells from the immune system to protect the body’s tissues from being infected or damaged.

Alpha-1 antitrypsin deficiency is caused by a genetic abnormality. The liver releases the protein to help protect the lungs from damage related to infections, smoking or inhalation irritants. If the liver can’t release the protein into the blood the correct way, the protein accumulates in the liver and causes injury.

The genetic abnormality is inherited from your parents. We can group people in the following ways depending on how much of the alpha-1 antitrypsin protein they make:

  • Normal (MM): These individuals make normal alpha-1 antitrypsin protein. They do not carry any abnormal genes and do not have the disease.
  • Carrier (MZ): These individuals have one abnormal allele which may lead to mild reductions in alpha-1 antitrypsin protein in the blood. While they are generally healthy, they are at risk of passing the abnormal allele to their children.
  • Carrier (MS): While these individuals carry an abnormal allele, they usually produce normal amounts of alpha-1 antitrypsin and are not at increased risk for developing liver or lung problems related to the disease. They are at risk of passing the abnormal allele to their children.
  • Alpha-1 antitrypsin deficiency (SZ): These individuals have a moderate deficiency of alpha-1 antitrypsin protein and are at risk for disease symptoms. They will pass one abnormal allele to each of their children.
  • Alpha-1 antitrypsin deficiency (ZZ): These individuals have severe deficiency of alpha-1 antitrypsin protein and are at the highest risk for developing liver and lung disease symptoms. They will pass one abnormal allele to each of their children.
  • Alpha-1 antitrypsin deficiency (SS): While these individuals carry two abnormal alleles, they often create enough alpha-1 antitrypsin to protect the lungs and are not considered at increased risk of developing disease symptoms.

Alpha-1 antitrypsin deficiency occurs worldwide, and it is common, affecting about 1 in 1,500-3,500 people of European ancestry. It is less common in Hispanic and Black populations and uncommon among Asian populations. It is estimated that worldwide, 185 million people are genetic carriers.

What are the signs of alpha-1 antitrypsin deficiency?

The signs and symptoms of alpha-1 antitrypsin deficiency vary based on the person’s genetic makeup, the amount of alpha-1 antitrypsin protein that is produced and which organ system is involved. Most people with the disease will start showing lung symptoms between the ages of 25 and 50 years. Lung damage from lack of the alpha-1 antitrypsin protein happens over time, most commonly beginning around age 30, and is highly accelerated by smoking.

Pulmonary, or lung, symptoms include:

  • Wheezing
  • Coughing
  • Shortness of breath
  • Coughing up phlegm or mucus
  • Fatigue
  • Chest pain

Signs and symptoms of liver damage are the most common indication of alpha-1 antitrypsin deficiency in infants and usually occur within the first two months of life, as jaundice and abnormal liver blood tests can confirm the presence of the deficiency. While many infants with alpha-1 antitrypsin deficiency liver disease will show improvement over time with supportive care, some will develop progressive liver injury that can result in the need for a liver transplant. Carriers of the disease are unlikely to develop signs or symptoms of alpha-1 antitrypsin deficiency and are often never diagnosed.

While the lungs and liver are the most common organs affected by alpha-1 antitrypsin deficiency, it can also cause a rare skin manifestation called panniculitis. Panniculitis is characterized by hardened skin and painful lumps or patches which could mean alpha-1 antitrypsin deficiency.

How does alpha-1 antitrypsin deficiency affect the lungs?

People with alpha-1 antitrypsin deficiency who make low levels of the protein do not have the appropriate protection in the air sacs of the lungs called “alveoli.’’ When the alveoli are damaged due to lack of alpha-1 antitrypsin protein, it leads to a lung disease called emphysema. Alpha-1 antitrypsin deficiency is the most common genetic risk factor for emphysema, and it is estimated that up to 3% of all people diagnosed with chronic obstructive pulmonary disease (COPD) may have undetected alpha-1 antitrypsin levels.

Smoking can cause COPD or emphysema on its own and can cause damage to the lungs in those with alpha-1 antitrypsin deficiency quicker than non-smokers. Symptoms of lung disease may start gradually and then worsen as the disease becomes more advanced.

Common symptoms of lung disease from alpha-1 antitrypsin deficiency include:

  • Shortness of breath
  • Wheezing
  • Dry cough
  • An abnormal appearance of the chest called a “barrel-shaped chest”
  • Recurrent chest infections
  • Abnormal pulmonary function testing which shows obstruction
  • Decreased oxygen levels

Diagnosis of alpha-1 antitrypsin deficiency in the lungs often starts with chest imaging and pulmonary function testing. Imaging could include either a plain chest x-ray or a CT scan of the chest which often reveals emphysematous changes in the lower zones of the lungs, or damage in the lower zones of the lungs that point to emphysema. The American Thoracic Society guidelines recommend smoking cessation and testing for alpha-1 antitrypsin deficiency for any patient diagnosed with emphysema, regardless of smoking status and especially for those younger adults.

How does alpha-1 antitrypsin deficiency affect the liver?

While the lung injury in alpha-1 antitrypsin deficiency is caused by a lack of alpha-1 antitrypsin in the lungs, the liver injury results from too much alpha-1 antitrypsin protein being trapped in the liver. Because of the buildup of this abnormal protein, the liver becomes irritated, which can lead to liver inflammation, scarring and sometimes dysfunction. Like smoking may speed up alpha-1 antitrypsin lung disease, viral infections of the liver, excessive consumption of alcohol and fatty liver disease may speed up alpha-1 antitrypsin liver injury.

How is alpha-1 antitrypsin deficiency diagnosed and treated?

Adults with emphysema, COPD or chronic bronchitis, patients with bronchiectasis (dilated small airways that lead to frequent infections), newborns, children or adults with unexplained liver disease, people with a family history of liver disease, those who have blood relatives with diagnosed alpha-1 and anyone with panniculitis should be tested for alpha-1 antitrypsin deficiency.

Testing involves a blood test or a mouth swab to check for genetic abnormalities. Blood tests are also available to determine the level of alpha-1 antitrypsin in the blood. Those with genetic abnormalities, emphysema, and low levels of alpha-1 antitrypsin in the blood can be treated with weekly intravenous infusions of blood plasma from healthy donors, which can increase the levels of alpha-1 antitrypsin protein in the patient. Given that alpha-1 antitrypsin deficiency is a genetic disease, there’s no way to prevent the disease if you have genetic variants. Focus should be on avoiding exposures that can increase damage to the lungs or liver, specifically smoking, excessive alcohol use or environmental and work exposures to harmful inhalation irritants (chemicals and dusts). Testing can also be offered as part of genetic counseling for those carriers or individuals with the disease who want to know the risk of passing the disease onto their children.

Ultimately, alpha-1 antitrypsin only rarely causes end-stage lung or liver damage. If a person develops end state lung disease or cirrhosis, organ transplantation can be considered. Depending on the circumstances, a person may only need individual lung or liver transplantation, while some patients may have severe disease that requires both lung and liver transplantation at the same time. Decisions about end-stage disease and transplantation are often made by multi-disciplinary teams which include pulmonologists, hepatologists and transplant teams.

Ochsner Health is proud to be an A1AT Foundation Clinical Resource Center, providing care to both children and adults with alpha-1 antitrypsin deficiency, as well as both liver and lung transplantation, if needed.

Meet your A1AT Foundation Clinical Resource Center team at Ochsner Children's:

Learn more about Ochsner Children's.

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