Alpha-1-antitrypsin deficiency

Alpha-1-antitrypsin deficiency is a hereditary metabolic disorder. It is the most common metabolic liver disease in children and results in the unopposed action of neutrophil elastase and subsequent severe basal emphysema and respiratory symptoms.

Clinical presentation

The classic presentation of the disease is with dyspnoea in the 4^th to 5^th decades of life.

Pathology

Alpha-1 antitrypsin (AAT) is a protein that prevents enzymes such as elastin from degrading normal host tissue. Over 90% of the alpha-1-antitrypsin protein is produced in hepatocytes by codominant gene expression on chromosome 14. The alpha-1-antitrypsin protein inhibits neutrophil elastase. In patients with severe deficiency, the neutrophil elastase acts unopposed resulting in damage to the lower respiratory tract. This damage is predominantly basal because of the gravitational distribution of pulmonary blood flow. 

Radiographic spectrum

Chest

Chest imaging findings include 

• pan-lobular emphysema - 
  • the emphysema pattern was traditionally thought to be pan-lobular although more recent studies have also suggested a variable pattern to the emphysema
  • emphysema may develop in 75-85% of cases ¹²
• bronchiectasis - may be seen in up to 40% of cases ⁹
• frank bullae formation ¹³ -  non specific feature
• bronchial wall thickening ¹³ - non specific feature
• hepatopulmonary syndrome 

Abdomen

Hepatic manifestations of this disease are those of cirrhosis with the concomitant increased risk of hepatocellular carcinoma. 

Treatment and prognosis

Emphysema and cirrhosis are usually considered the most common causes of death ⁸.

Survival is substantially worse in smokers, who have a  -20 year decrease in longevity relative to non-smokers. According to one study, the overall median survival time was ~ 55 years ⁷.

AAT replacement therapy, most often by weekly intravenous infusions of AAT purified from human plasma, has been used in some situations to partially correct the biochemical defect ^14-15.  

While randomized, placebo-controlled clinical trials have confirmed a reduction in the decline in lung density in patients receiving augmentation therapy ¹⁴. It's efficacy in reducing mortality however is uncertain ¹⁶. Other management strategies include avoidance of smoking and other risk factors for cirrhosis.

Differential diagnosis

The differential will depend upon the the organ involved

• for thoracic manifestations - see differential for panlobular emphysema
• for hepatic manifestions - see differential for cirrhosis