Alpha-1 Antitrypsin Deficiency

Alpha-1 Antitrypsin Deficiency

Overview

Alpha-1 antitrypsin deficiency (sometimes just called “Alpha-1”) is an inherited genetic disorder that causes low levels of a protein (AAT) that protects your lungs. Alpha-1 increases your risk of developing certain diseases, including emphysema (damaged air sacs in your lungs), cirrhosis (liver scarring) and panniculitis (an uncommon skin condition). Some of these conditions can be life-threatening.

Alpha-1 is sometimes referred to as “genetic COPD” or “genetic emphysema.”

Alpha-1 antitrypsin deficiency affects people who have two copies of the SERPINA1 gene that makes an abnormal type of the Alpha-1 protein. Genes are the instructions for how your body should function.

These gene changes can cause your body to have low levels of AAT or no AAT in your lungs, and, depending on the changes, a buildup of AAT in your liver. Any of these changes can cause health issues. People with one abnormal copy of the gene and one normal copy (called Alpha-1 carriers) can also have symptoms and are at an increased risk of lung damage, especially if they smoke.

Alpha-1 is one of the most common genetic disorders among those with European ancestry, but it’s uncommon in people of non-European descent. One in 25 people of European descent have at least one abnormal copy of the gene for Alpha-1. In 1 in about 3,500 people in the U.S., both of their genes for AAT are abnormal, putting them at risk for severe organ damage. About 75% of people with two malfunctioning genes will eventually develop lung function issues.

Alpha-1 antitrypsin (AAT) is a protein that forms in your liver and moves through your bloodstream to your lungs. It’s the “off switch” for an enzyme called neutrophil elastase. Neutrophil elastase is important for fighting infections in your lungs, but it can also destroy your healthy lung tissue. After elastase has had time to help fight an infection, AAT shuts it off (inhibits) so it won’t damage your lungs.

If a gene mutation causes low levels of AAT or creates incorrectly formed AAT, you won’t have enough in your lungs to stop elastase, which will start breaking down the protein elastin in your lungs. Elastin gives strength to the small air sacs of your lungs (alveoli) and allows them to stretch and contract, like a rubber band. Without it, your alveoli lose their shape and become floppy. This makes it so you can’t breathe or get oxygen properly. This is a condition called emphysema.

Gene mutations that change the shape of AAT keep it from moving out of your liver. It builds up there and can cause scarring. Since it can’t get out of your liver, it’s not able to move to your bloodstream and your lungs.

Alpha-1 isn’t necessarily a terminal illness. Many people with Alpha-1, especially if they don’t smoke, can live a normal life span.

Symptoms

Lung diseases caused by Alpha-1 have symptoms similar to chronic obstructive pulmonary disease (COPD). Lung symptoms usually start between the ages of 30 and 50 and include:

Shortness of breath (dyspnea), especially with exercise or exertion.

A whistling sound when you breathe (wheezing).

Chronic cough, often with mucus.

Extreme tiredness.

Frequent chest colds.

About 10% of infants and 15% of adults with Alpha-1 develop liver disease. Signs and symptoms of liver disease may include:

Yellowing of the skin and eyes (jaundice).

Itchy skin.

Swelling in your legs or abdomen (ascites).

Throwing up blood.

Rarely, your first symptoms of Alpha-1 are painful, red bumps on your skin (panniculitis). These can move around on your body and may break open, leaking fluid or pus.

Causes

Everyone has two sets of genes (the instructions for how your body functions), one from each parent. Just like differences in these instructions can determine what color eyes or hair you have, they can also change how your body functions. Differences (mutations) in a specific gene cause Alpha-1 antitrypsin deficiency.

The SERPINA1 gene makes a protein called Alpha-1 antitrypsin (AAT) that protects your lungs from damage caused by another protein in your body (neutrophil elastase, which attacks infections in your lungs). There are many SERPINA1 mutations that can change how your body makes AAT. Some tell your body to make less AAT, some tell your body not to make any at all, and some cause AAT to form incorrectly so it can’t get to your lungs. Any of these can cause you to have too little AAT in your lungs to protect them.

If both copies of your SERPINA1 gene have mutations, you have Alpha-1 antitrypsin deficiency. Depending on the types of abnormal genes, you have a 75% chance of developing lung symptoms. If you have a mutation in just one of your copies of the gene (carrier), your body can usually make enough functioning AAT to protect your lungs. You’re still at an increased risk for lung damage and could eventually develop symptoms, especially if you smoke.

Alpha-1 inheritance

Carriers of abnormal Alpha-1 genes can pass the mutation on to their children. If both parents are carriers, their children have a 25% chance of having two abnormal genes and a 50% chance of being carriers (one abnormal copy and one normal copy). Since both genes contribute to how you make AAT rather than one being dominant, Alpha-1 antitrypsin deficiency is said to have a codominant inheritance.

Diagnosis

A provider diagnoses Alpha-1 with blood tests. Because it has symptoms of other illnesses, sometimes it can take a long time to diagnose Alpha-1. You might be tested for Alpha-1 if you have liver symptoms or if you’ve received a COPD diagnosis. Tests and procedures your provider might perform include:

Blood tests. A provider takes a sample of your blood to measure your levels of AAT and understand how well your liver is working. If you have low levels of AAT, they’ll do genetic testing to identify gene differences associated with Alpha-1.

Imaging. X-rays and CT scans can show signs of Alpha-1 in your lungs and rule out other conditions. These tests can show the location of any damage and how severe it is.

Pulmonary function tests. These tests can’t diagnose Alpha-1, but they can tell your provider how well your lungs are working. They often involve breathing into a machine that measures your lung function.

Liver ultrasound or elastography. If your provider suspects issues with your liver, they may get a liver ultrasound or elastography ultrasound (FibroScan®) to see if there’s any scarring.

Liver biopsy. If you have liver damage, your provider may take a small sample of tissue (biopsy) from your liver to determine how severe the damage is.

Treatment

For those with lung conditions from Alpha-1, your provider can treat you with COPD medications and therapies, like bronchodilators and pulmonary rehabilitation. If you have emphysema due to very low levels of Alpha-1 in your blood, they may recommend augmentation therapy. Augmentation therapy delivers normal Alpha-1, collected and purified from blood donors, through an IV. Augmentation therapy can slow the progression of emphysema.

If Alpha-1 affects your liver, your provider may be able to treat some of the symptoms, but only a liver transplant can cure Alpha-1 by restoring normal AAT production.

Not smoking or drinking reduces your risk of lung and liver damage from Alpha-1. It’s recommended that you get vaccinated to help prevent viral hepatitis and pneumonia.

Depending on where Alpha-1 affects you, treatment options may include:

Augmentation therapy. Your provider can increase your AAT levels by giving you supplemental normal AAT (collected and purified from blood donors) directly into a vein (IV infusion). This can’t reverse lung damage but can prevent future damage. It doesn’t prevent liver damage from Alpha-1.

Medication. Inhaled corticosteroids and bronchodilators can make it easier to breathe by reducing inflammation and opening your airways.

Oxygen therapy. If your oxygen levels are low, your provider may prescribe supplemental oxygen, which a machine delivers through a mask on your face or through small tubes in your nose.

Pulmonary rehabilitation. Breathing exercises and physical therapy can make breathing easier.

Smoking cessation therapy. If you smoke, your provider can recommend therapies to help you quit.

Lung transplant. If your lungs are severely damaged, getting a healthy lung through a transplant can help improve your quality of life.

Liver transplant. If your liver is badly scarred, your provider may recommend a liver transplant. A healthy liver should make normal AAT.

Type of Doctor Department : Pulmonologists, Gastroenterologists ,Geneticists