What are the other Names for this Condition? (Also known as/Synonyms)

• A1AD (Alpha-1 Antitrypsin Deficiency)
• Hereditary Pulmonary Emphysema
• Inherited Emphysema

What is Alpha-1 Antitrypsin Deficiency? (Definition/Background Information)

• Alpha-1 Antitrypsin Deficiency (AATD) is a genetic disorder inherited in an autosomal recessive manner, in which there is deficiency of the protein alpha-1 antitrypsin (AAT) in blood
• In the body, AAT functions to protect the lungs. However, when it is not present in adequate amounts, the lungs can be damaged resulting in breathing difficulties
• Normally, alpha-1 antitrypsin is produced in the liver and subsequently released into the bloodstream. Due to certain mutations, the SERPINA1 gene is unable to provide instructions for making the AAT protein
• Environmental factors, including exposure to tobacco smoke, chemicals, and dust can also contribute to lung damage in individuals with Alpha-1 Antitrypsin Deficiency, so individuals with only one cope of defective gene are also at risk of developing the disease if they are exposed to these toxins
• The signs and symptoms associated with Alpha-1 Antitrypsin Deficiency are shortness of breath, wheezing, asthma, fatigue, jaundice, and unintentional weight loss. The complications of AATD may include liver cirrhosis and emphysema
• The blood levels of alpha-1 antitrypsin enzyme may be evaluated to diagnose this deficiency disorder. The treatment includes intravenous replacement of alpha-1 antitrypsin enzyme
• With certain lifestyle modifications and appropriate treatment of symptoms, most individuals with Alpha-1 Antitrypsin Deficiency can  live normal lives

Who gets Alpha-1 Antitrypsin Deficiency? (Age and Sex Distribution)

• Alpha-1 Antitrypsin Deficiency can affect both males and females, at an incident rate of approximately 1 in 2500 individuals
• While it is found in all ethnic groups, individuals of European ancestry have been more frequently observed to have this deficiency condition
• The affected individuals are born with the disorder; however, environmental factors can increase severity of the symptoms and the age at which they manifest. Most individuals with Alpha-1 Antitrypsin Deficiency begin to manifest symptoms between the ages of 20-50 years

What are the Risk Factors for Alpha-1 Antitrypsin Deficiency? (Predisposing Factors)

• Alpha-1 Antitrypsin Deficiency is an inherited genetic disorder with an autosomal recessive pattern. This means that both copies of the genes (from each parent) must be mutated to develop the condition
• If the child inherits only one copy of the mutated genes, then he/she becomes a carrier. Such individuals produce lower than normal levels of alpha-1 antitrypsin, but enough to enable the lungs to function normally. Typically, such carriers will not show any signs or symptoms

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one's chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Alpha-1 Antitrypsin Deficiency? (Etiology)

Alpha-1 Antitrypsin Deficiency is caused by mutations in the SERPINA1 gene.

• A normally functioning SERPINA1 gene provides instructions for making the alpha-1 antitrypsin (AAT) protein. This protein protects the body from the neutrophil elastase enzyme. While this enzyme is beneficial to the body, as it fights infections, it can also attack normal tissues if it is not controlled by alpha-1 antitrypsin
• When mutations are present on the gene, a deficiency of alpha-1 antitrypsin occurs or an abnormal form of the protein is created. In both cases, neutrophil elastase cannot be controlled and attacks normal tissues such as the lungs. This can lead to breathing problems, and in more severe cases, lung disease
• Alpha-1 Antitrypsin Deficiency is an autosomal recessive condition. If mutations are present on only one copy of the gene, the individual is usually able to produce enough alpha-1 antitrypsin to have normally functioning lungs
• Abnormal AAT can also accumulate in the liver and damage the organ, causing liver disease

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Alpha-1 Antitrypsin Deficiency?

The common signs and symptoms of Alpha-1 Antitrypsin Deficiency include:

• Shortness of breath, wheezing, and asthma
• Chronic bronchitis -  inflammation of the airways
• Reduced ability to exercise
• Lung infections
• Fatigue
• Unintentional weight loss
• Emphysema - destruction of air spaces (alveoli) in the lungs
• Jaundice
• Liver cirrhosis (liver fibrosis) and liver failure
• Panniculitis (that occurs in rare cases)

How is Alpha-1 Antitrypsin Deficiency Diagnosed?

The diagnosis of Alpha-1 Antitrypsin Deficiency may include:

• A complete evaluation of medical history along with a thorough physical exam
• Blood levels of alpha-1 antitrypsin
• Chest x-ray
• CT scan chest
• Pulmonary function test
• Liver function test
• Genetic testing to determine the individual’s genotype, to see if they have mutations in the SERPINA1 gene

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Alpha-1 Antitrypsin Deficiency?

The potential complications of Alpha-1 Antitrypsin Deficiency may include:

• Emphysema: Abnormal permanent enlargement of air spaces in the lungs
• Bronchiectasis - destruction and widening of airways
• Liver failure or even liver cancer

How is Alpha-1 Antitrypsin Deficiency Treated?

The treatment measures for Alpha-1 Antitrypsin Deficiency may include:

• Intravenous (through vein) replacement of alpha-1 antitrypsin enzyme
• Lung transplants, in cases of severely damaged lungs or with end-stage lung disease
• Antibiotics and bronchodilators are given for respiratory infections

Researchers are also currently experimenting with gene therapy, where the patient is administered the healthy gene through a modified virus. This virus, if it functions correctly, can cause the patient to start producing the normal gene, allowing for normal production of the alpha-1 antitrypsin protein.

Newer medications to alter the effects of abnormal proteins using RNA interference (RNAi) and other molecular technologies are in various stages of development and commercialization. The medical provider may help with information on advancements in new treatment methods.

How can Alpha-1 Antitrypsin Deficiency be Prevented?

Currently, there are no specific methods or guidelines to prevent Alpha-1 Antitrypsin Deficiency, since it is a genetic condition.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis of Alpha-1 Antitrypsin Deficiency? (Outcomes/Resolutions)

• Most symptoms of Alpha-1 Antitrypsin Deficiency do not arise until the individual is between the age of 20 and 50 years
• With certain lifestyle behavior (such as smoking cessation) and appropriate symptomatic treatment, most individuals can lead a normal quality of life
• The prognosis of AATD is not good, if emphysema and liver cirrhosis develops

Additional and Relevant Useful Information for Alpha-1 Antitrypsin Deficiency:

• The alpha-1 antitrypsin test helps determine the amount of AAT in the bloodstream and is an early indicator of health risk for children, due to liver dysfunction

The following article link will help you understand alpha-1 antitrypsin test:

https://www.dovemed.com/common-procedures/procedures-laboratory/alpha-1-antitrypsin-test/