How often should I have lung function testing if I have AAT deficiency but feel fine?

Even without symptoms, most specialists recommend baseline spirometry at diagnosis and then repeat every 1–2 years to track any early decline, especially if you smoke or have occupational exposures.

What happens if I continue to smoke or am exposed to second‑hand smoke?

Smoking dramatically accelerates lung damage in AAT deficiency; even occasional exposure can increase the risk of early emphysema. Complete cessation and avoidance of polluted environments are strongly advised.

If my liver enzymes become abnormal, what treatment options are available?

Mild enzyme elevations are usually monitored, but progressive cirrhosis may require referral for hepatology evaluation, possible use of ursodeoxycholic acid, and ultimately liver transplantation. Regular imaging for hepatocellular carcinoma is also recommended.

How is the diagnosis confirmed and what does genetic testing involve?

definitive diagnosis combines a low serum AAT level (usually <57 mg/dL) with phenotyping or genotyping. Genetic testing identifies the common Z and S alleles and any rare variants, guiding prognosis and family counseling.

Alpha-1 antitrypsin deficiency

Alpha-1 antitrypsin deficiency is an inherited genetic disorder that significantly increases the risk of developing progressive lung and liver diseases, such as emphysema and cirrhosis.

Overview & Symptoms

Alpha-1 antitrypsin deficiency is an inherited disorder that may cause lung disease and liver disease. The signs and symptoms of the condition, as well as the age at which they appear, vary among individuals.

People with this condition usually develop the first signs and symptoms of lung disease between ages 25 and 50. The earliest symptoms include:

Shortness of breath following mild activity
Reduced ability to exercise
Wheezing
Unintentional weight loss
Recurring respiratory infections
Fatigue

Affected individuals often develop emphysema, a lung disease caused by damage to the small air sacs in the lungs (alveoli). Characteristic features of emphysema include difficulty breathing, a hacking cough, and a barrel-shaped chest. Smoking or exposure to tobacco smoke accelerates the appearance of emphysema symptoms and lung damage.

Liver disease develops in about 10 percent of infants with alpha-1 antitrypsin deficiency, often causing yellowing of the skin and whites of the eyes (jaundice). Approximately 15 percent of adults with the condition develop liver damage (cirrhosis) due to the formation of scar tissue in the liver. Signs of cirrhosis include a swollen abdomen and jaundice. Affected individuals are also at risk of developing a type of liver cancer called hepatocellular carcinoma.

In rare cases, people with alpha-1 antitrypsin deficiency develop a skin condition called panniculitis, which is characterized by hardened skin with painful lumps or patches. Panniculitis varies in severity and can occur at any age.

Frequency

Alpha-1 antitrypsin deficiency occurs worldwide, but its prevalence varies by population. This disorder affects about 1 in 1,500 to 3,500 individuals of European ancestry. It is uncommon in people of Asian descent. Many individuals with alpha-1 antitrypsin deficiency are likely undiagnosed, particularly those with chronic obstructive pulmonary disease (COPD). While COPD can be caused by alpha-1 antitrypsin deficiency, the underlying genetic deficiency is often never diagnosed. Some affected individuals are misdiagnosed with asthma.

Causes & Risk Factors

Variants (also known as mutations) in the SERPINA1 gene cause alpha-1 antitrypsin deficiency. This gene provides instructions for making a protein called alpha-1 antitrypsin, which protects the body from a powerful enzyme called neutrophil elastase. Neutrophil elastase is released from white blood cells to fight infection, but it can attack normal tissues—especially the lungs—if not tightly controlled by alpha-1 antitrypsin.

Variants in the SERPINA1 gene can lead to a shortage (deficiency) of alpha-1 antitrypsin or an abnormal form of the protein that cannot control neutrophil elastase. Without enough functional alpha-1 antitrypsin, neutrophil elastase destroys alveoli and causes lung disease. Abnormal alpha-1 antitrypsin can also accumulate in and damage the liver.

Environmental factors, such as exposure to tobacco smoke, chemicals, and dust, likely impact the severity of the condition.

Inheritance

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 have two copies of the M allele (MM) in each cell. Other versions of the gene lead to reduced levels of the protein:

The S allele produces moderately low levels of alpha-1 antitrypsin.
The Z allele produces very little alpha-1 antitrypsin.

Individuals with two copies of the Z allele (ZZ) in each cell have a high risk of developing emphysema and liver disease. Those with the SZ combination have an increased risk of developing lung disease, particularly if they smoke.

Worldwide, an estimated 185 million people carry one copy of the S or Z allele and one copy of the M allele (MS or MZ). Individuals with an MS (or SS) combination usually produce enough alpha-1 antitrypsin to protect their lungs. However, people with MZ alleles have a slightly increased risk of impaired lung or liver function.

Other Names for This Condition

AAT
AATD
Alpha-1 protease inhibitor deficiency
Alpha-1 related emphysema
Genetic emphysema
Hereditary pulmonary emphysema
Inherited emphysema