Alpha-1 antitrypsin deficiency(AATD) is a rare genetic disease that causes lung, liver, and skin problems. The liver synthesizes alpha-1 antitrypsin protein (AAT) then releases it into the blood to protect your lungs and all organs against proteolytic enzymes and any irritant materials. Also, it has anti-inflammatory action. AATD is equal in males and females and most common in white people.
The cause of AATD is the inheritance of a mutated gene from your parents. When you take a mutated gene from both of your parents, you will be at a higher risk of AATD.
AATD patients may be asymptomatic until 20-50 years or for all life. In AAT deficiency, proteolytic enzymes attack your lungs, which destructs the elastic tissue of the lung. The patient complains of a shortening of breath, cough, wheezing, and rapid tiredness. Also, the patient may complain of loss of weight and allergy. In AAT deficiency, AAT accumulates in the liver, which leads to liver damage. Liver disease may develop in infants, children, or adults with AATD. In infants, there are jaundice, cholestasis, hepatomegaly, and ascites. Symptoms of children are loss of weight, edema, portal hypertension, and liver failure. Symptoms of adults are hepatites, portal hypertension, cirrhosis, and liver carcinoma. Also, there are skin manifestations.
We can diagnose AATD by measuring AAT levels in the blood and genetic tests. Also, we use imaging techniques to see the symptoms and exclude other possible causes.
Treatment of AATD isn’t curative; it just reduces complications and helps to live a healthy life. Doctors give you AAT intravenous to increase its level in the blood. You also may need a bronchodilator and oxygen therapy. In late cases, doctors may need to do lung or liver transplantation. You can’t prevent AATD, but You can reduce complications by avoiding smoking and any irritant substances.
Now, let’s see this disease in more detail. We will discuss the following:
- What causes this disease, and who is at risk of having it?
- What are its symptoms, signs, and advanced complications?
- How will my doctor diagnose if I have this disease and confirm this diagnosis?
- How can my doctor treat me, and what are the treatment options that I have?
- How can I prevent or reduce its complications?
- What is the prognosis of AATD?
Cause of alpha-1 antitrypsin deficiency
The direct cause of AATD is a mutation in the SERPINA-1 gene. This gene synthesizes AAT, which protects our body against neutrophil elastase enzyme, and has an anti-inflammatory effect. There are more than 150 SERPINA-1 gene mutations, but the most common are S and Z alleles. M allele is the healthy form of the gene. S allele means that the AAT level range from moderate to low. Z allele means that the AAT level is severely low. There are some mutations in which the level of AAT in the blood reaches zero.
You would be at high risk of AATD disease if you received two abnormal genes from both parents. Also, there is more risk of AATD disease if the two abnormal genes are Z alleles (ZZ). The site of the SERPINA-1 gene isn’t on sex chromosomes; thus, the risk is equal in males and females. It lies on the long arm of chromosome 14. For the carrier parents, the risk of pregnancy with a ZZ infant is 25% and 50% to get a carrier baby. If you received one Z allele from one parent and the other gene is normal (MZ), you would be at a small risk of AATD, but smoking increases the risk. Also, SZ is less severe than ZZ, but smoking increases the severity.