Supporting Australian Alphas since 2002

How is Alpha-1 Diagnosed?

Although Alpha-1 is one of the most common genetic disorders in the world, it is often misdiagnosed. Many times patients are told they have asthma, bronchitis, symptoms related to stress, emphysema caused by smoking, or simply chronic obstructive pulmonary disease of unknown cause.

The most common indicators of Alpha-1 include shortness of breath, a chronic cough, and abnormal liver test results. If you have any of these symptoms there is a simple blood test that can detect alpha-1 antitrypsin levels. This test is also recommended if you have relatives, especially siblings, who have been diagnosed with alpha-1, or if there is a family history of early emphysema, with or without smoking.

The laboratory test measures alpha-1 antitrypsin levels in blood, which are usually reported within Australia using grams per litre (g/L), however alternative measures are milligrams per 100 ml (mg%) and micromoles per liter (µM/L). All measurements provide the same basic information on how much alpha-1 antitrypsin is in the blood.

People with two healthy copies of the alpha-1 gene produce the most alpha-1 antitrypsin, and people with no copies of the gene at all produce the least. In addition, environmental factors can affect how much alpha-1 antitrypsin is in the blood. An individual's genetic makeup (genotype) combines with environmental factors to determine their phenotype. Here are the more common phenotypes and their corresponding blood alpha-1 levels.

Phenotype

g/L

mg%

µM/L

MM (two normal copies)

1.10 - 3.50

110 - 350

20.2 - 64.4

MZ (one normal copy, one deficient copy)

0.74 - 2.10

74 - 210

13.6 - 38.6

SS (two marginally deficient copies)

1.00 - 2.00

100 - 200

18.4 - 36.8

SZ (one deficient copy, one marginally deficient copy)

0.75 - 1.20

75 - 120

13.8 - 22.1

ZZ (two deficient copies)

0.20 - 0.45

20 - 45

3.68 - 8.28

NULL (two nonfunctional copies)

0

0

0

Table data source: American Thoracic Society / European Respiratory Society Statement: Standards for the Diagnosis and Management of Individuals with Alpha-1 Antitrypsin Deficiency > page 925 > Table 3, adjusted where test results are known for Australian patients.

 

Alpha-1 levels of 0.8 g/L (80 mg% or 14.7 µM/L) or less put you at greatest risk of developing alpha-1 related emphysema. Smokers with intermediate deficiency levels (0.80 to 1.60 g/L) are also at increased risk of lung disease.

Of 13 testing laboratories around Australia, as at 3 December 2016 the published reference ranges for Alpha-1 Antitrypsin levels had an average low of 0.94 g/L, and an average high of 1.98 g/L.

A couple of user-friendly online conversion calculators exist:

In the table above, M refers to the normal gene. Over 75 combinations of gene variations (alleles) have been identified, some of which can cause Alpha-1. The S, Z and Null genes are the most common ones that cause alpha-1 deficiencies. ZZ is the most common allele that causes lung disease.

The Null gene is one that produces no detectable levels of alpha-1. Alphas with the Null-Null phenotype are at the greatest risk of developing emphysema, yet none have suffered liver damage as a result of their Alpha-1

For more information on Alpha-1 testing, please see page numbered 5 of the AAA booklet. You may also find helpful:

Booklets

 The AAA has produced an information booklet which contains more detail about A1AD, and a poster for raising awareness. You can access the booklet and poster by clicking on the images below. The poster may be printed locally in A3 or A4 size. Please encourage your family doctor or respiratory physician to put a poster on display in the surgery or patient waiting area! For more information about A1AD, see our Links section.