Alpha-1 Antitrypsin Deficiency (AATD)


Alpha-1 Antitrypsin Deficiency (AATD) is a rare, inherited genetic condition with a global incidence of 1 in every 1500 to 3500 individuals with European ancestry.1 It is one of the most common, potentially lethal, rare diseases affecting primarily those of European descent, although all ethnicities can be affected.2 AATD affects the liver and lungs, depending on which type of AATD is inherited.

Patient Education Mission

Patient education is critical to understanding AATD so that the diagnosed individuals, called Alphas, and their families can adhere to the recommendations and preventative measures to lead a longer, healthier and more productive life.3 It is important for the newly diagnosed individual and all immediate and extended family members to be aware that this condition is passed down from one’s parents and can be passed down to future children as well. Family genetic testing is important to determine who else in the family has AATD and who is a carrier of the mutated gene. This testing should also include spouses who have married into the family of an individual with AATD to identify if they are also carriers of the condition. Genetic counseling is available to help couples make informed decisions about the risk of passing on this condition. It is important for individuals with AATD to understand the nature of the condition so that they make educated lifestyle choices that reduce progression of the disease.

Genetics of AATD

AATD has an autosomal codominant mode of inheritance. This means that each parent must pass along a mutated gene for the child to inherit AATD. The normal gene is called the M gene. The most common abnormal genes are called the Z and S genes. Individuals with a normal M gene and abnormal Z or S gene are called carriers. Individuals who inherit AATD can have parents that either are both carriers, one is a carrier while the other may have AATD, or both parents could have AATD.3 The more severe manifestations of AATD coincide with the inheritance of the Z gene.4 If both parents have AATD, there is a 100% likelihood of their child inheriting the disorder. If both parents are carriers, there is a 25% chance that their child may inherit the disorder, a 25% chance that their child will not have AATD, and a 50% chance that their child will also be a carrier. This disease is not sex-linked, so it occurs equally among women and men.5  

Infant Screening

AATD is one of the leading causes of inherited liver disease in infants and children, and the second most common cause for liver transplantation in children.6 AATD has the potential to progress to end-stage liver failure, acute liver failure, or liver cancer which can be life-threatening.6 Although it is not standardized, but it is important for newborns who have unremitting jaundice to be immediately tested for AATD. It is also important to immediately test newborns born to parents who both are known carriers of a mutated gene. This prompt testing of newborns can allow doctors and parents to make the best decisions for the baby’s health to prevent progression of liver disease, and for the child in question to be educated early on lifestyle choices that will prevent the future acceleration of lung disease as an adult.7

Disease Progression in Adults

It is important that individuals diagnosed with AATD understand that the lack of normal production of the alpha-1 antitrypsin (AAT) protein may cause deterioration of the lungs. The lung tissue is not protected from the destruction of a particular enzyme which is usually inhibited by AAT. This may lead to symptoms of lung disorders like emphysema, chronic obstructive pulmonary disease (COPD), asthma, chronic bronchitis, or bronchiectasis.3 These lung symptoms are usually seen in adults aged 20-50, but typically are seen in clinics during the fourth decade of life.1 

Lifestyle Recommendations 

Patient education for AATD includes specific lifestyle recommendations.3,8 There are two different categories of patient education for AATD – things to actively avoid and things to do proactively to live the healthiest and fullest possible life.

Things to avoid include:

  • Smoking, including e-cigarettes, to avoid progression of lung disease
  • Alcohol intake to prevent progression of liver disease and cirrhosis
  • Second-hand smoke at work, at home, and in the community (restaurants, hotels, etc)
  • High-risk occupations where particulate, chemical, or gas inhalation (organic or inorganic) may accelerate lung disease
    • Organic dust includes hay, coal, etc
    • Irritating gases include chlorine, isocyanates, etc
  • Environmental pollutants such as pesticides, pollen, dust, pet dander, and aerosol sprays that can irritate the lungs 
  • Chemicals (such as chlorine and ammonia which are found in common home cleaning products), which can be absorbed through the skin and damage the liver or can be inhaled and damage the lungs
  • Respiratory irritants from wood-burning stoves or fireplaces
  • Contact with sick or infectious people as recurrent bacterial or viral infections are harmful to the lungs
  • High sodium diets which may increase fluid retention
  • High fat and high protein diets that may be difficult to process with liver disease
  • Processed foods that have little nutritional value and are typically high in sodium and sugar
  • Specific supplements that might tax the liver more

Things to do include:

  • Stop smoking 
  • Limit or abstain from alcohol if there is evidence of liver disease
  • Request clean indoor air with proper ventilation and filtration systems at work
  • Wear protective, rubber gloves when using household cleaners to reduce skin contact, but it is best to avoid household chemical cleaners entirely 
  • Frequently wash hands with soap and water to prevent contracting or spreading infectious diseases 
  • Use antibacterial hand gel when hand washing is not possible
  • Participate in a routine exercise program to improve lung capacity and endurance, to maintain strength especially of the respiratory muscles, and to boost psychological state. 
  • Obtain guidance from a healthcare provider or exercise trainer to effectively monitor the exercise progression and to slowly build intensity to tolerance
  • Walk indoors in a climate-controlled environment (i.e. shopping malls), cycle indoors, or swim in indoor pools to improve lung function and stamina
  • Participate in a Pulmonary Rehabilitation Exercise Program (PREP), which includes nutrition counseling, breathing retraining, patient education, smoking cessation, and development of an exercise routine to achieve optimal quality of life and activity level
  • Participate in stress reduction techniques for relaxation and to combat depression
  • Consult with a nutrition specialist who will develop an appropriate nutrition plan 
  • Obtain protein from plant-based sources like nuts, beans, and tofu, instead of animal sources, since protein is important for lung function8
  • Be current with vaccinations especially annual flu vaccines to prevent further damage to the lungs and the hepatitis A and B vaccines to prevent further damage to the liver 

Resources for Patients

Organizations such as Alpha-1 National Association, AlphaNet, and Alpha-1 Foundation offer patient, family, and caregiver education materials, access to support groups and networking on a national level, telephone hotlines (1-800-4ALPHA-1 through the Alpha-1 National Association and 1-866-For-A1AA through the Alpha-1 Advocacy Alliance), and opportunities to participate in research studies.8 

References

  1. Alpha-1 antitrypsin deficiency. Medline Plus Genetics. Accessed June 7, 2021.
  2. Anariba, DEI. Alpha1- antitrypsin deficiency: etiology. Medscape. Accessed on June 7, 2021.
  3. Alpha-1 recently diagnosed brochure. Alpha-1 Foundation. Accessed June 7, 2021.
  4. Stoller JK, Hupertz V, Aboussouan LS. Alpha-1 antitrypsin deficiency. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews.® University of Washington, Seattle; 1993. Accessed June 7, 2021.
  5. Alpha-1 antitrypsin deficiency. National Organization for Rare Diseases (NORD). Accessed June 7, 2021.
  6. Spada M, Riva S, Maggiore G, Cintorino D, Gridelli B. Pediatric liver transplantation. World J Gastroenterol. 2009;15(6):648-674. doi:10.3748/wjg.15.648
  7. Tretter JT. Adding α-1 antitrypsin deficiency to the newborn screen. Journal of Pediatric Gastroenterology and Nutrition. 2015; 60(4):e37. doi:10.1097/MPG.0000000000000720
  8. Anariba, DEI. Alpha-1 antitrypsin deficiency: Patient education. Medscape. Accessed June 7, 2021.

Article reviewed by Harshi Dhingra, MD on July 1, 2021.

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