What to Know About Alpha-1 Antitrypsin Deficiency (AATD)

Medically Reviewed By William C. Lloyd III, MD, FACS

Alpha-1 antitrypsin deficiency (AATD) is a genetic condition characterized by low levels of the protein alpha-1 antitrypsin. AATD can increase the likelihood of other conditions, including liver and lung diseases. The blood contains the alpha-1 antitrypsin (AAT) protein. Not enough AAT allows substances known as proteolytic enzymes to damage different body tissues, resulting in further health conditions.

Treatment to infuse AAT into the body can effectively address some types of AATD. Treatment for related conditions that AATD can cause may also improve the outlook.

This article discusses AATD, including its related conditions, symptoms, and diagnosis. It also explains the causes, treatment, and outlook of AATD.

Types

A family with two children sit in the garden of a house.
Maskot/Getty Images

There are four basic types Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source of AATD:

  • Normal: This indicates typical levels of AAT and typical function.
  • Deficient: AAT levels in the blood are less than 35% of the average typical level.
  • Null: There is no detectable AAT protein in the blood. This is the least common type of AATD, and it may lead to severe lung disease rather than liver disease.
  • Dysfunctional: There is a typical amount of AAT, but it does not function effectively.
A medical illustration of the possible complications of AATD.
Illustrated by Wenzdai Figueroa

AATD can damage the lungs, liver, and skin, increasing the risk of developing other health conditions. According to the National Organization for Rare Disorders (NORD), AATD most commonly leads to:

  • chronic obstructive pulmonary disease (COPD), including bronchitis and emphysema
  • liver diseases, such as:
    • cirrhosis, scarring of the liver
    • hepatoma, liver tumors

Less commonly, AATD may lead to:

However, AATD does not necessarily lead to further conditions.

Symptoms

There are no set AATD symptoms. People may not experience noticeable symptoms of the deficiency itself or know they have AATD without testing.

Instead, people may experience symptoms of the conditions AATD causes. Adults usually develop these symptoms between the ages of 20–50 years.

How AATD progresses and the symptoms it causes can vary. Typically, adults experience symptoms of lung disease before symptoms of other conditions.

Symptoms of lung conditions associated with AATD may include:

  • shortness of breath
  • difficulty taking deep breaths
  • wheezing
  • chronic or persistent cough
  • excess phlegm
  • frequent respiratory infections

Some lung conditions linked to AATD are slow, progressive conditions. As a result, these symptoms may develop gradually over time.

Symptoms of liver conditions associated with AATD include:

  • fatigue
  • jaundice, yellowness or discoloration of the skin
  • dark urine and pale or bloody stools
  • itching
  • enlarged liver, possibly causing a protrusion or swelling in the abdomen
  • ease of bleeding or bruising
  • decrease in appetite
  • swelling of the legs or stomach
  • impaired growth or failure to thrive in infants

Liver conditions linked to AATD may develop at any time from infancy to adulthood.

Symptoms of skin conditions associated with AATD may include:

  • itching
  • swelling of the skin
  • rash or hives
  • skin discoloration
  • dry or scaly patches of skin
  • ulcers or broken skin that may leak blood or other fluids
  • fever
  • symptoms of panniculitis, such as nodules, small lumps, beneath the skin that:
    • appear after injury
    • are tender
    • appear red, discolored, or have an irregular border
    • are swollen or feel hardened

Panniculitis may develop at any age.

Causes

AATD is an inheritable genetic condition, meaning it can be passed on through biological family members. The gene SERPINA1 is responsible for producing AAT. Changes, or mutations, in the gene cause AATD.

AATD has a codominant inheritance pattern. This means a person may develop AATD by inheriting two copies of a mutated gene, one from each biological parent.

Genes, including SERPINA1, can have many versions, or alleles. The severity of AATD and the conditions it causes can depend on which allele of the SERPINA1 gene is inherited. For example, inheriting two copies of the Z allele of SERPINA1 may increase the risk of developing emphysema.

Some people can carry genetic changes without developing the condition. When two parents carry one copy of the same allele, the chances of having a child with AATD is 25% with each pregnancy. The chances of having a child with no genetic changes and no AATD is also about 25% each time. There is a 50% chance that each child carries the genetic changes but has no AATD.

According to a 2023 overview, clinicians consider AATD to be rare Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source . However, it is possible that the condition is underdiagnosed.

Risk factors

Some factors may worsen Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source AATD or increase the likelihood of conditions such as COPD. These factors include:

  • smoking and exposure to tobacco smoke
  • exposure to:
    • certain chemicals
    • dust
    • other pollutants, including industrial products

The following risk factors may lead to a higher risk of emphysema:

  • family history of COPD
  • history of conditions such as:

When to see a doctor

Contact your doctor promptly if you develop symptoms that are new, persistent, or go away and then come back.

Call 911 or your local emergency services for any of these symptoms:

Testing and diagnosis

Lung, liver, or skin conditions can have causes other than AATD.

Tests for AATD may include Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source blood tests for AAT levels. Doctors may also recommend genetic testing to identify the specific type of AATD. In some cases, your doctor may recommend genetic counseling for your immediate biological family members.

Your doctor may use additional methods to diagnose conditions that can develop as a result of AATD. Your doctor may ask about your symptoms, medical history, and your family medical history. Because AATD and related conditions such as COPD are inheritable, inform your doctor if family members have been diagnosed with them.

Your doctor may also conduct a physical exam. Other diagnostic tools can include:

  • chest X-rays
  • CT scans
  • breathing and lung function tests, such as a spirometry test

Treatment

Doctors may recommend AAT augmentation therapy to treat AATD. This is a long-term treatment of regular infusions of purified AAT from donated blood. People often receive this treatment once every week.

Doctors may also prescribe medications known as alpha-1 proteinase inhibitors, such as:

  • Aralast NP
  • Zemaira
  • Prolastin-C
  • Glassia

NORD suggests that AAT augmentation therapy may be effective in slowing the progression of lung conditions related to AATD. However, the therapy is not effective for AATD-related liver disease. Doctors may not recommend AAT augmentation therapy for everyone.

Doctors may recommend additional treatments for health conditions that develop as a result of AATD.

Read more about treatments for COPD and liver disease.

Preventing complications

Not all complications of AATD are preventable. However, you may be able to reduce the risks of developing certain conditions.

Approaches to protect your health and reduce risks can include:

  • not smoking
  • limiting alcohol
  • receiving vaccinations to prevent infection
  • eating a healthful diet, as recommended by your doctor or a licensed dietitian
  • maintaining a moderate weight
  • following your doctor’s instructions for treatment
  • contacting your doctor for new or persistent symptoms of illness
  • having regular checkups

Outlook

The outlook for AATD depends on the type of AATD, your genetic profile, and any related conditions that develop. For example, the outlook may be worse Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source for people who develop liver cirrhosis.

Following your doctor’s recommended treatment can help improve your outlook. Also, being aware of the increased risk of developing other conditions can help you take steps to protect your health.

Contact your doctor for personal advice about your treatment and outlook with AATD.

Summary

AATD is an inheritable condition associated with low levels of the AAT protein. Having AATD can increase the risk of developing conditions such as COPD, liver cirrhosis, and panniculitis.

Symptoms of AATD include symptoms of the conditions it can cause. For example, COPD symptoms may include persistent cough, wheezing, and shortness of breath.

Treatment for AATD may include medication, AAT infusions, and lifestyle changes.

Contact your doctor promptly for new or persistent symptoms of illness.

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Medical Reviewer: William C. Lloyd III, MD, FACS
Last Review Date: 2023 May 30
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