Alpha-1 Antitrypsin Deficiency (AATD)

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Alpha-1 antitrypsin deficiency (AATD) is an inherited, genetic disorder characterized by liver and pulmonary disease. The symptoms of AATD, their severity, and the age of onset vary among individuals and the different types of AATD.1 Ordinarily, liver disease presents at a younger age and lung disease presents later in life, usually in individuals between the ages of 20 and 50.1

Symptoms of AATD in infants

The first sign of possible AATD in infants is jaundice at birth that does not disappear.2 Jaundice is indicative of liver disease, cholestasis or obstruction of the bile duct, or excessive hemolysis.1 It is usually the first sign of liver disease, and it sometimes can be the only sign.3

Symptoms of AATD in children

Symptoms of AATD liver disease in children include jaundice, pale stools, dark urine, elevated liver enzymes, severe itching, splenomegaly, ascites, and easy bleeding or bruising.2 

Pale stools indicate the absence of bile which is normally released by the liver into stool, giving stool its brown color. When the bile duct is blocked or there is liver disease, bile is not properly released into the stool, leaving them pale or clay-colored.4 Dark urine indicates the presence of bilirubin, which is excreted by the kidneys in the urine.3 

Elevated liver enzymes indicate inflammation or damage to the liver cells. These injured liver cells leak higher than normal amounts of liver enzymes and other chemicals into the bloodstream. The liver enzymes most commonly identified in routine blood tests include alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transpeptidase (GGT).5

The accumulation of bile salts underneath the skin causes severe pruritus in liver disease, which may be widespread or localized.6

Splenomegaly is another indicator of liver disease. Scarring and damage to the liver impedes the movement of blood through the liver, causing this blood to back up in the portal venous system, resulting in portal hypertension. This backflow of blood results in the spleen becoming engorged with blood, leading to splenomegaly.7 

Fluid leaking from the surface of the damaged liver and mesenteric vessels can cause ascites, usually in the setting of portal hypertension in liver disease.3 

In addition, damaged liver cells struggle to produce enough clotting factors, which results in the symptoms of easy bleeding or bruising.8 

Symptoms of AATD in Adults

Adults with AATD can also manifest the symptoms of liver disease as mentioned above. As the disease progresses and begins to negatively affect lung function, the symptoms of AATD in adults manifest as wheezing, shortness of breath, reduced exercise tolerance, fatigue, recurrent pulmonary infections, chronic cough producing sputum, a barrel-shaped chest, positional tachycardia, cyanosis, visual changes, and unintentional weight loss.9,10

Wheezing results from inflammation that causes a narrowing or restriction of airways. Wheezing is commonly observed in chronic obstructive pulmonary disease (COPD) and asthma due to bronchospasms or constrictions of the small airways of the lungs.11 Due to the destruction of lung tissue and concurrent inflammation, AATD can lead to the development of COPD, emphysema, or chronic bronchitis, all of which can contribute to wheezing. 

Dyspnea becomes apparent in individuals with AATD, most frequently in early adulthood, and usually after mild to moderate exercise. Specifically, these patients present with a feeling of suffocating, air hunger, general difficulty breathing, or a tightness in the chest and lungs.12 In AATD, destruction of the alveoli impedes gas exchange from occurring. When people with AATD exercise, they are unable to get adequate oxygen into their lungs commensurate with their activity level. 

Individuals with AATD have recurrent lung infections due to lack of healthy lung tissue and an inability to clear the lungs of the infection quickly, allowing the virus or bacteria to grow more rapidly than in a person with healthy lung tissue. This eventually may lead to development of a chronic productive cough. This often is diagnosed as chronic bronchitis.13 

Often individuals with COPD and emphysema develop a barrel chest. This refers to a broad, deep, round chest found in individuals with chronic lung diseases. The lungs become chronically overinflated with air to compensate for the decreased rate of gas exchange occurring in the alveoli. This overinflation causes the rib cage to expand in all directions and remain  this way, making breathing less efficient.14

In the later stages of chronic obstructive pulmonary disease associated with AATD, positional tachycardia is often presented. In these cases, the heart must pump faster to circulate necessary oxygen in the blood to the brain and body with positional changes when gravity causes most of the blood to pool in the lower extremity veins. A more serious symptom of this severe lack of oxygen in the bloodstream is cyanosis.15  

A 2017 study published in the peer-reviewed journal PLOS One revealed that individuals with COPD demonstrate hypoxia in the central nervous system blood vessels compared with healthy controls.16 Severe COPD can impact adequate oxygen delivery to the retina and optic nerves. Over time, these microvascular changes may negatively affect vision in those with AATD and COPD.17 

Weight loss signals severe COPD with AATD progression. As the lungs expand outward creating the barrel chest, they also press downward into the diaphragm, which pushes down on the stomach. A flattened diaphragm makes it more difficult to breathe. This extra pressure against the stomach makes eating uncomfortable because as the food enters the stomach, it also expands pushing against the diaphragm. This makes it even harder to breathe, and may trigger bloating or indigestion. Often, people with advanced AATD and COPD are discouraged from regular, healthy eating because of these problems, which results in weight loss.18

Rare Symptoms in AATD

Among the rarer symptoms of AATD, panniculitis is a skin condition causing hardened bumps and patches that develop on the skin. These bumps irritate the subcutaneous fat layer of the skin called the panniculus, causing it to become inflamed. Panniculitis varies in severity and occurs at any age.19  

References

  1. Alpha-1 antitrypsin deficiency. Medline Plus. Accessed May 27, 2021.
  2. Alpha-1 antitrypsin deficiency. Boston Children’s Hospital. Accessed May 27, 2021.
  3. Common characteristics of liver disease. Johns Hopkins Medicine. Accessed May 27, 2021.
  4. Pale stools: possible causes and when to seek help. Healthline. Accessed May 27, 2021.
  5. Symptoms: elevated liver enzymes. Mayo Clinic. Accessed May 27, 2021.
  6. What causes itching in liver disease and how to treat it. Healthline. Accessed May 27, 2021.
  7. Mavrogiannis, M. Splenomegaly: what is it, causes, severity, diagnosis, treatment, and more. Osmosis. Accessed May 27, 2021.
  8. Liver damage symptoms your doctor wants you to know about. Texas Digestive Disease Consultants. Accessed May 27, 2021.
  9. What is alpha-1? Patient guide. Alpha-1 Foundation. Accessed May 27, 2021.
  10. Alpha-1 antitrypsin deficiency (AATD). Cedars-Sinai. Accessed May 27, 2021.
  11. Symptoms: wheezing. Mayo Clinic. Accessed May 27, 2021.
  12. Symptoms: shortness of breath. Mayo Clinic. Accessed May 27, 2021.
  13. Chronic bronchitis overview. WebMD. Accessed May 27, 2021.
  14. Barrel chest: what causes it? Mayo Clinic. Accessed May 27, 2021.
  15. Chronic obstructive pulmonary disease. Amboss. Accessed May 27, 2021.
  16. Eliasdottir TS, Bragason D, Hardarson SH, et al. Retinal oximetry measures systemic hypoxia in central nervous system vessels in chronic obstructive pulmonary disease. PLoS One. 2017;12(3):e0174026. Published 2017 Mar 22. doi:10.1371/journal.pone.0174026
  17. Can COPD affect the eyes? Kadrmas Eye Care New England. Accessed May 27, 2021.
  18. The link between COPD and weight loss. Healthline. Accessed May 27, 2021.
  19. What is panniculitis? Healthline. Accessed May 27, 2021.

Article reviewed by Kyle Habet, MD, on July 1, 2021.

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