Alpha 1-antitrypsin deficiency (α1-antitrypsin deficiency, A1AD) is a genetic disorder that causes defective production of alpha 1-antitrypsin (A1AT), leading to decreased A1AT activity in the blood and lungs, and deposition of excessive abnormal A1AT protein in liver cells.Alpha-1 antitrypsin deficiency is an inherited disorder that can cause lung disease in adults and liver disease in adults and children. Alpha-1 antitrypsin (AAT) is a protein that protects the lungs. The liver makes it. If the AAT proteins aren't the right shape, they get stuck in the liver cells and can't reach the lungs.ALPHA 1-ANTITRYPSIN DEFICIENCY
Signs and symptomsWhat are the signs and symptoms of lung disease caused by alpha-1 antitrypsin deficiency?
Symptoms of AAT deficiency include
- Tiredness
- Shortness of breath and wheezing
- Vision problems
- Repeated lung infections
- Rapid heartbeat upon standing
- Some people have no symptoms and do not develop complications.
- Weight loss
Associated conditions
Conditions associated with Alpha-1 Antitrypsin Deficiency, occurring due to insufficiency of AAT in circulation allowing uninhibited inflammation in lungs, and accumulation of mutated AAT in the Liver.
α1-antitrypsin deficiency has been associated with a number of diseases:
- Bronchiectasis
- Cirrhosis
- Pneumothorax
- COPD
- Granulomatosis with polyangiitis
- Asthma
- Gallstones
- Pelvic organ prolapse
- Pancreatitis
- Autoimmune hepatitis
- Primary sclerosing cholangitis
- Secondary Membranoproliferative Glomerulonephritis
- Emphysema, predominantly involving the lower lobes and causing bullae
- Hepatocellular carcinoma (liver)
- Cancer
- Gallbladder cancer
- Bladder carcinoma
- Lung cancer
- Lymphoma
What genes are related to alpha-1 antitrypsin deficiency?
Mutations in the SERPINA1 gene cause alpha-1 antitrypsin deficiency.
The SERPINA1 gene provides instructions for making a protein called alpha-1 antitrypsin. This protein protects the body from being damaged by a powerful enzyme called neutrophil elastase. Neutrophil elastase is released from white blood cells to fight infection, but it can attack normal tissues (such as lung tissue) if not carefully controlled by alpha-1 antitrypsin. Mutations in the SERPINA1 gene can lead to a shortage (deficiency) of alpha-1 antitrypsin protein or an abnormal form of the protein that cannot control neutrophil elastase. Uncontrolled, neutrophil elastase destroys alveoli, which can lead to emphysema. The abnormal form of alpha-1 antitrypsin can also accumulate in the liver and may damage this organ.
How do people inherit alpha-1 antitrypsin deficiency?
This condition is inherited in an autosomal codominant pattern. Codominance means that two different versions of the gene may be active (expressed), and both versions contribute to the genetic trait.
The most common version (allele) of the SERPINA1 gene, called M, produces normal levels of alpha-1 antitrypsin. Most people in the general population have two copies of the M allele (MM) in each cell. Other versions of the SERPINA1 gene lead to reduced levels of alpha-1 antitrypsin. For example, the S allele produces moderately low levels of this protein, and the Z allele produces very little alpha-1 antitrypsin. Individuals with two copies of the Z allele (ZZ) in each cell are likely to have alpha-1 antitrypsin deficiency. Those with the SZ combination have an increased risk of developing lung diseases (such as emphysema), particularly if they smoke.
Worldwide, it is estimated that 161 million people have one copy of the S or Z allele and one copy of the M allele in each cell (MS or MZ). Individuals with an MS (or SS) combination usually produce enough alpha-1 antitrypsin to protect the lungs. People with MZ alleles, however, have a slightly increased risk of impaired lung or liver function.
What other names do people use for alpha-1 antitrypsin deficiency?
Diagnosis-How Is Alpha-1 Antitrypsin Deficiency Diagnosed?
Alpha-1 antitrypsin (AAT) deficiency usually is diagnosed after you develop a lung or liver disease that's related to the condition.
Diagnostic Tests
Your doctor may recommend tests to confirm a diagnosis of AAT deficiency. He or she also may recommend tests to check for lung- or liver-related conditions.
- A blood test also may be used. This test checks the level of AAT protein in your blood. If the level is a lot lower than normal, it's likely that you have AAT deficiency.
- A genetic test is the most certain way to check for AAT deficiency. This test will show whether you have faulty AAT genes.
Lung-Related Tests
If you have a lung disease related to AAT deficiency, your doctor may recommend lung function tests and high-resolution computed tomography (to-MOG-rah-fee) scanning, also called CT scanning.
- Lung function tests measure how much air you can breathe in and out, how fast you can breathe air out, and how well your lungs deliver oxygen to your blood. These tests may show how severe your lung disease is and how well treatment is working.
- High-resolution CT scanning uses x rays to create detailed pictures of parts of the body. A CT scan can show whether you have emphysema or another lung disease and how severe it is.
What is COPD?
- COPD is the abbreviation for chronic obstructive pulmonary disease.
A1AT deficiency remains undiagnosed in many patients. Patients are usually labelled as having COPD without an underlying cause. It is estimated that about 1% of all COPD patients actually have A1AT deficiency. Thus, testing should be performed for all patients with COPD, asthma with irreversible air-flow obstruction, unexplained liver disease, or necrotizing panniculitis. The initial test performed is serum A1AT level. A low level of A1AT confirms the diagnosis and further assessment with A1AT protein phenotyping and A1AT genotyping should be carried out subsequently.
How Is Alpha-1 Antitrypsin Deficiency Treated?
Alpha-1 antitrypsin (AAT) deficiency has no cure, but its related lung diseases have many treatments. Most of these treatments are the same as the ones used for a lung disease called COPD (chronic obstructive pulmonary disease).
If you have symptoms related to AAT deficiency, your doctor may recommend:
- Flu and pneumococcal (noo-mo-KOK-al) vaccines to protect you from illnesses that could make your condition worse. Prompt treatment of lung infections also can help protect your lungs.
- Pulmonary rehabilitation (rehab). Rehab involves treatment by a team of experts at a special clinic. In rehab, you'll learn how to manage your condition and function at your best.
- Extra oxygen, if needed.
- Medicines called inhaled bronchodilators and inhaled steroids. These medicines help open your airways and make breathing easier. They also are used to treat asthma and COPD.
- A lung transplant. A lung transplant may be an option if you have severe breathing problems. If you have a good chance of surviving the transplant surgery, you may be a candidate for it.
- Augmentation therapy is a treatment used only for people who have AAT-related lung diseases. This therapy involves getting infusions of the AAT protein. The infusions raise the level of the protein in your blood and lungs.
Preventions-How Can Alpha-1 Antitrypsin Deficiency Be Prevented?
You can't prevent alpha-1 antitrypsin (AAT) deficiency because the condition is inherited (passed from parents to children through genes).If you inherit two faulty AAT genes, you'll have AAT deficiency. Even so, you may never develop one of the diseases related to the condition.
You can take steps to prevent or delay lung diseases related to AAT deficiency. One important step is to quit smoking. If you don't smoke, don't start.
Avoid smoke and places with dust, fumes, or other toxic substances that you may inhale.