What is Alpha-One Antitrypsin Deficiency?

Alpha-One Antitrypsen (AATD or Alpha-1) Deficiency is genetic condition that is passed from parents to their children, and can lead to serious lung disease in adults and liver disease at any age. For each trait that a person inherits from their parents, there are usually two genes - one from each parent. People who have Alpha-1 have received two abnormal alpha-1 antitrypsin genes.

Read more about genetic disorders.

For people with Alpha-1 Antitrypsan Deficiency low to zero amounts of A1AT are found in the blood. A1AT is a protein created in the liver, released into the blood stream and used to protect the lungs from neutrophil elastase, which is an enzyme that can disrupt connective tissues. Neutrophil elastase is created by the white blood cells in response to infections or irritants, to digest damaged tissues in the lungs.

Without enough Alpha-One antitrypsin, the lungs may be damaged, which makes breathing more difficult.

There are several forms and degrees of Alpha-1, which primarily depends upon whether the person has inherited one or two copies of the abnormal gene.

AATD is a fairly rare genetic disorder; approximately one in 2,500 people are diagnosed with this disorder, over all ethnic groups, but most commonly found in whites of European ancestry. Alpha-1 is the most common genetic cause of liver disease in children.

Who Gets Alpha-1 Antitrypsin Deficiency?

Alpha-1 has been identified in nearly all populations and ethnic groups; it's estimated that 1 in every 2,500 Americans have Alpha-1.

Approximately 19 million people in the US have one normal and one abnormal Alpha-1 gene. Those who have one normal and one abnormal Alpha-1 gene are known as "carriers" of Alpha-1. These genetic carriers may pass the disease onto their children.

Most people who have Alpha-1 are healthy throughout their lives. Early diagnosis and avoiding the risk factors for the disease (like smoking) can help people who have Alpha-1 from causing disease.

The lung destruction from Alpha-1 is often first diagnosed as asthma or smoking-related COPD (Chronic Obstructive Pulmonary Disease). Up to 3% of people who have been diagnosed with COPD may have undiagnosed Alpha-1. Alpha-1 is the most commonly known genetic risk factor for emphysema.

What Causes Alpha-One Antitrypsin Deficiency?

Alpha-One Antitrypsin Deficiency is an inherited condition in which one or both of the AAT genes are damaged. Generally, people inherit two normal copies of the gene for AAT and are unaffected by Alpha-One Antitrypsin Deficiency. Those who are diagnosed with Alpha-One Antitrypsin Deficiency inherit one or two damaged AAT genes from one or both of their parents.

In the case of one damaged AAT gene, a person is often able to function normally with no interference in breathing, particularly if that individual is a non-smoker.

People with two damaged AAT genes are prone to more severe symptoms.

How Alpha-1 Antitrypsan is Inherited:

Alpha-1 Antitrypsin deficiency is inherited in families in an autosomal codominant pattern - meaning that two different variants of the gene may be expressed, and both versions contribute to the genetic trait.

The M gene is the most common allele of the alpha-1 gene. It produces normal levels of the alpha-1 antitrypsin protein.

The Z gene is the most common variant of the gene. It causes alpha-1 antitrypsin deficiency. The S allele is another, less common variant that causes ATTD.

If a person inherits one M gene and one Z gene or one S gene ('type PiMZ' or 'type PiMS'), that person is a carrier of the disorder. While such a person may not have normal levels of alpha-1 antitrypsin, there should be enough AAT to protect the lungs. However, carriers with the MZ alleles have an increased risk for lung disease, particularly if they smoke.

A person who inherits the Z gene from each parent is called 'type PiZZ.' This person has very low alpha-1 antitrypsin levels, allowing elastase - an enzyme especially of pancreatic juice that digests elastin - to damage the lungs. A person who inherits an altered version called S and Z is also likely to develop AATD.

 What are the Symptoms of Alpha-One Antitrypsin Deficiency?

Alpha-1 damages the small air sacs - the aveoli - of the lungs, which means that the damaged aveoli are not able to expand and contract as efficiently as they would in a normal person. This means that a person with Alpha-1 cannot breathe as normally as others. People with Alpha-1 often feel short of breath, they may wheeze, or cough. As the lungs deteriorate further, the person with Alpha-1 may develop lung diseases such as asthma, emphysema, or chronic bronchitis.

Approximately 10% of infants and 15% of adults with Alpha-1 have liver damage, which can progress into chronic liver disease, cirrhosis. Rarely, people with Alpha-1 develop hard and painful lumps under their skin called "panniculitis."

Alpha-One Antitrypsin Deficiency may present as lung disease in adults or as liver disease in children with AATD.

In newborns, the typical symptoms of Alpha-1 are jaundice, a swollen abdomen, and poor feeding. Alpha-1 can appear in late childhood or early adulthood based upon findings of poor appetite, fatigue, swelling of the legs and abdomen, or abnormal liver panel tests.

Damage to the lungs can make breathing more difficult, and cause other lung-related diseases and disorders. For example, some individuals with AATD are also diagnosed with lung disease and emphysema. AATD is a form of inherited emphysema.

Other lung symptoms of Alpha-1 Antitrypsin Deficiency may include:

  • Difficulty breathing
  • Wheezing
  • Respiratory infections
  • Fatigue
  • Rapid heartbeat upon standing
  • Vision problems
  • Unintentional weight loss
  • Hacking cough
  • Barrel-shaped chest
  • Exercise intolerance
  • Year-round allergies
  • Brochiectasis
  • Chronic obstructive pulmonary disease (COPD)
  • Asthma
  • Chronic bronchitis

Other liver symptoms may include:

  • Unexplained liver disease
  • Elevated liver enzymes
  • Jaundice (yellowed sclera of the eyes or skin)
  • Ascites - swelling of the abdomen or legs
  • Vomiting blood (from enlarged veins in the stomach or esophagus)

These symptoms may worsen as the disease progresses.

Although all ages are affected, most symptoms begin between the ages of 20 to 40.

How is Alpha-One Antitrypsin Diagnosed?

Many times, Alpha-1 is misdiagnosed as the symptoms mimic those of less serious conditions, like asthma, stress, bronchitis, chronic obstructive pulmonary disease, and smoking-induced emphysema. If you have the hallmark symptoms: dyspnea, chronic cough, and abnormal liver enzyme results, don't hesitate to ask your doctor to perform a blood test to determine if you have Alpha-1.

A physical examination may check for chest shape, wheezing, crackles, or decreased breath sounds. If there's a genetic history, Alpha-1 is diagnosed via a blood test, upon onset of Alpha-1 symptoms. These blood tests include:

Alpha-1 Genotyping - this test examines a person's genes and determines their genotype.

Alpha-1 Antitrypsin PI - this test is a type of phenotype test and identifies the type of AAT protein that a person has.

Alpha-1 Antitrypsin Level Test - ascertains the amount of AAT in a person's blood.

Individuals who have symptoms that suggest AATD or who have a family history of AATD should consider being tested before symptoms appear, in order to ensure that the disease is properly managed.

Other examinations and diagnostic tools to measure both lung and liver function include: chest x-rays, pulmonary function tests, lung volume measurements, as well as laboratory blood tests to check liver function.

How Is Alpha-One Antitrypsin Deficiency Treated?

Alpha-1 is a genetic condition that currently has no cure. Treatment of Alpha-1 is focused upon the prevention and slowing the progression of both lung disease and liver damage.

Doctors attempt to increase the amount of alpha-1 antitrypsin in the blood of a person with Alpha-1 via augmentation therapy. People with Alpha-1 are given a weekly injection of alpha-1 antitrypsin from the blood of a healthy person. While augmentation therapy does not aim to cure Alpha-1 Antitrypsin Deficiency, it can slow the progression of the disease.

Other treatments include:

  • Antibiotics to treat any respiratory infections that may occur as the disease progresses.
  • Bronchodilators are often used to treat lung symptoms like asthma.
  • Corticosteroids are also used to treat asthma or other lung symptoms.
  • Oxygen treatment may help a person with lung disease to help them breathe more easily.
  • Surgery - including lung and liver transplant - to replace the diseased lungs with normal lungs.

Currently, researchers are experimenting with gene therapy, in which a person with Alpha-1 is given a healthy copy of the gene using a modified virus, which "infects" the cells of a person with the disease to have them produce the normal gene.

Tips for Living With Alpha-One Antitrypsin Deficiency:

One of the biggest concerns for people who have Alpha-1 is staying healthy.

Read more about living while immunocompromised.

There are a variety of tips and preventative measures that are available and believed to help, if you suffer from Alpha-1:

  • Quit smoking.
  • Drink alcohol with caution (if at all). Drinking alcohol can cause liver damage, which people who have Alpha-1 are already prone to developing.
  • Stay indoors and avoid poor air quality.
  • Wash hands as regularly as possible. If a sink is not available, use antibacterial hand gel.
  • The feelings of those who are diagnosed with a chronic illness can range from anger, to fear, to sadness.
  • When you are out of breath, it's a very scary feeling. Know that it's okay to be afraid.
  • You may be afraid of losing your control over your life. Talk about your fears with a closed friend or loved one.
  • Write about your experiences, either via a journal or here on Band Back Together.
  • It's okay to not be okay - when you're having a bad day, don't be afraid to call off work and do something to take care of you.
  • Find a hobby that brings you a sense of satisfaction that requires less physical exertion. Knitting, doing crafts, keeping a blog, writing for fun are all great low-stress activities.
  • Lower your stresses as much as you can. Some stresses are a normal part of life, but your whole life doesn't have to be stressful.
  • Find a caregiver if you are ill, and don't hesitate to ask for help when you need some.
  • Exercise regularly
  • Get flu and pneumonia vaccines as soon as possible
  • Avoid alcohol in large amounts
  • Find a healthcare team that works for you and keep all appoints with your team. Regular healthcare is a must.
  • Avoid dust. Wear a mask, even for tasks like vacuuming and sweeping.
  • Find and join a support group in your area for people with similar conditions. Support groups are a great way to find people going through what you're going through as well as find and develop new coping mechanisms. 
  • If you find yourself becoming depressed and unable to cope with your illness, find a therapist to talk to about your feelings. Remember, all feelings are normal - even the ugly ones.
  • Don't give up.

Related Resource Pages on Band Back Together:

Asthma

Caregiver

Chronic Illness

Cirrhosis

Genetic Diseases

Immunodeficiency

Liver Disease

Living While Immunocompromised

Living With Chronic Illness

Additional Resources for Alpha-One Antitrypsin Deficiency:

The Alpha-1 Foundation provides a newly diagnosed guide.

Alpha1.org is an information hub and resource center for information about AATD.