History and exam

Key diagnostic factors

common

The National Heart, Lung, and Blood Institute (NHLBI) Registry of Individuals with Severe Deficiency of AAT reported 50% of patients with cough.[55] Many patients meet criteria for chronic bronchitis, manifested as chronic cough for 3 months in 2 successive years.[52]

Patients with respiratory disease may present with shortness of breath on exertion.

The greatest risk factor for emphysema in patients with the PI*ZZ phenotype is smoking. Lung function and survival are both affected.[24][46]​​​[47]​​​​ Some evidence suggests that ex-smokers and people who have never smoked have similar declines in lung function over time.[48] Some smokers may never develop pulmonary symptoms.[42]

uncommon

Occupational or other exposure to inhaled toxins has been associated with decreased pulmonary function in patients with PI*ZZ AAT deficiency. This includes passive smoking and work with kerosene heaters.[49][50][51][52]

Patients with liver manifestations may present with hepatomegaly.

Patients with liver manifestations may present with ascites.

Patients with liver manifestations may present with hepatic encephalopathy.

Other diagnostic factors

common

This is the mean age at which smokers with AAT deficiency typically present with symptomatic pulmonary disease.[24]

At least one study has shown an increase in symptomatic lung disease in PI*ZZ males.[20] However, this result is likely to be confounded by other variables, such as smoking and occupational exposure.[21][22][23]

The NHLBI registry implies that bronchodilator-responsive wheezing is more prevalent in patients with deficient AAT than in patients with normal AAT and COPD.[55] However, it is neither sensitive nor specific for AAT-deficiency lung disease.[9]

Pulmonary function tests (PFTs) can differentiate between asthma and AAT deficiency disease because asthma is fully reversible with bronchodilation, whereas in AAT deficiency the reversibility is incomplete.[56]

May indicate the presence of respiratory disease.

uncommon

AAT deficiency causing liver failure will normally present as jaundice, indicating hepatitis.[57] Liver disease will only occur in patients with phenotypes that are associated with intrahepatic polymerisation of the AAT variant: notably the Z, Mmalton, and Siiyama.[12]

May indicate the presence of liver disease.

Risk factors

strong

The inheritance pattern of AAT deficiency is autosomal, and expression of the alleles is codominant. Knowledge that one or both parents are AAT deficient should increase suspicion of AAT deficiency, for example in an individual with early-onset emphysema.

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