GeneFacts

Thursday, Oct 23rd

Last update07:29:48 PM GMT

You are here: Diagnosis

Diagnosis

Print PDF

When diagnosis is suspected, measure serum level of alpha-1 antitrypsin; if low do genotyping (see Genetics)

Diagnostic Testing and Evaluation

Diagnostic criteria

Serum level of alpha-1 antitrypsin (AAT) <83 mg/dL
AND EITHER:

  • Demonstration of abnormal AAT protein by protease inhibitor (PI) typing

OR

  • Detection of mutations in both copies of the gene encoding alpha1-antitrypsin.

First Diagnostic Steps

History:

  • Family history of COPD or liver disease
  • Early onset COPD/chronic bronchitis, especially in absence of environmental triggers/exposures
  • Signs of cirrhosis in early childhood
  • Diagnosis of hepatocellular carcinoma (HCC) without cirrhosis or other obvious cause
  • Any adult with necrotizing panniculitis
  • Patients with unexplained liver disease

Diagnostic Tests:

  • AAT serum level
  • AAT isoelectric focusing (IE)
  • AAT genotypic testing

Testing Strategy

IE is less expensive than targeted mutation analysis and can reveal a range of allele variants, including rarer forms that may be missed with mutation analysis. If IE does not reveal an abnormality but clinical suspicion is high, sequence analysis may be used to identify the presence of disease-associated alleles

Tests that are not Helpful

Liver biopsy is not routinely recommended without evidence of liver disease or hepatocellular carcinoma.

Subsequent Diagnostic Evaluation

AATD confirmed patients: If signs of liver disease, biopsy may be useful to ascertain the extent of disease.

Lifestyle/Environmental Contributors to Disease

  • Smoking: Active and passive exposure further increases risk of COPD
  • Occupational exposure to environmental pollutants, gas, fumes, mineral dust

Differential Diagnosis

Conditions with similar clinical exams

  • Smoking-related COPD
  • Alcoholic cirrhosis
  • Hepatitis-related cirrhosis
  • Hepatocellular carcinoma from alcoholic cirrhosis or hepatitis infection

Conditions with similar laboratory findings

none

Consensus Statements and Guidelines

American Thoracic Society and European Respiratory Society

Alpha 1- antitrypsin deficiency: A position statement of the Canadian Thoracic Society