Alpha-1 antitrypsin deficiency is a disease caused by reduced or abnormal production in the body of the enzyme inhibitor alpha-1 antitrypsin. Body tissues and blood normally contain powerful enzymes - known as proteases - that can attack foreign substances within the body that may be harmful, such as tobacco smoke.

However, these protease enzymes must be carefully regulated as they could attack and damage normal tissues rather than the intended target resulting in local tissue damage.

Blood and tissues have a protease inhibitor that binds the enzyme to prevent unrestricted and potentially harmful protease activity. The commonest protease inhibitor in the blood is alpha-1 antitrypsin and its role is to protect the tissues from protease attack.

Alpha-1 antitrypsin is one of a family of proteins with similar functions known as the serine proteinase inhibitor (or serpin) superfamily. These proteins play an important role in controlling inflammation, coagulation and repair mechanisms in the body. Most alpha-1 antitrypsin in the body is produced by the liver. The liver is also damaged by alpha-1 antitrypsin deficiency, as are the lungs.

Respiratory (lung) disease
The lack of alpha-1 antitrypsin leads to progressive lung damage by protease enzymes, especially when combined with other factors such as smoking.
Alpha-1 antitrypsin deficiency causes emphysema, a chronic progressive lung disease caused by destruction of lung tissue and permanent abnormal enlargement of airspaces. The abnormal airspaces tend to be at the base of the lungs. Affected people, especially smokers, complain of shortness of breath and a cough. This shortness of breath initially occurs only on exertion but can lead to difficulty breathing at rest. This usually occurs over 15-20 years, but can lead to respiratory failure and premature death.

Hepatic (liver) disease
In PiZZ people (at risk of severe liver disease), defective alpha-1 antitrypsin molecules tend to clump together in the liver cells producing toxic effects.

Childhood liver disease
Alpha-1 antitrypsin deficiency is the most common genetic or inherited cause of liver disease in infants and children. The first signs are often jaundice, pale stools, excessive bleeding or an enlarged liver - all non-specific signs of liver disease. This is described as 'neonatal hepatitis syndrome' and usually begins between four days and six weeks after birth. A few babies rapidly develop liver failure and cirrhosis.
Most infants will improve, with jaundice fading and liver blood tests returning towards normal, so urgent treatment is not required. In later childhood, patients with alpha-1 antitrypsin deficiency may develop signs of chronic liver disease and liver failure. Some may have had jaundice or other liver problems after birth. The symptoms are the same as any other liver disease: abdominal pain, jaundice, itching, swelling of the ankles or abdomen and enlargement of the liver or spleen.
In severe cases bleeding from the gut, or drowsiness and coma, can cause complications...

Adult liver disease
The symptoms of liver disease due to alpha-1 antitrypsin deficiency in adults are similar to those in older children. But the disease may not become apparent for years. The symptoms are the same as with any other liver cirrhosis: jaundice, abdominal swelling, bleeding into the gut and, ultimately, coma. Alpha-1 antitrypsin deficiency is associated with an increased risk of hepato-cellular carcinoma or primary liver cancer. This cancer may be the first sign of disease.

Disease in alpha-1 antitrypsin carriers
It is unclear whether heterozygous carriers, eg those with one abnormal gene, are more prone to develop liver disease. Some liver disease currently of unknown cause may be due to alpha-1 antitrypsin deficiency. Alternatively, reduced alpha-1 antitrypsin may worsen or increase susceptibility to liver disease due to other causes such as infection or alcohol.

Emphysema
Cirrhosis