Alpha-1-antitrypsin (AAT) 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.
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The classic presentation of the disease is with dyspnoea in the 4th to 5th decades of life. Two-thirds of individuals show clinical features but most carriers are asymptomatic.
AAT is a protein that prevents enzymes such as elastase from degrading normal host tissue. Over 90% of the AAT protein is produced in hepatocytes by codominant gene expression on chromosome 14. The AAT 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.
- cirrhosis with increased risk of hepatocellular carcinoma 19
- AAT deficiency carriers are at 70-100% increased risk of lung cancer 20
Radiograph and CT
- 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: up to 40% 9
- frank bullae formation: non-specific feature 13
- bronchial wall thickening: non-specific feature 13
- hepatopulmonary syndrome
Reduced perfusion and ventilation in the lower zones on a V/Q study.
Hepatic manifestations of this disease are those of cirrhosis.
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 randomised, 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.
The differential will depend on the organ involved:
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