Applications

1628 – Alpha-1-Antitrypsin Genotyping

Find out about the service or technology in this application and the medical condition it addresses. You can also view the application documents, the deadlines for providing consultation input and the outcome of the application when the MSAC process is complete.

  • Status Complete
  • Type New application
  • Pre-PASC consultation -
  • Pre-MSAC consultation -
  • Outcome Not supported

Application details

Reason for application

New MBS item.

Service or technology in this application

Gene panel testing to identify alpha-1-antitrypsin (AAT) pathogenic variants in serum where the patient has respiratory symptoms indicative of AAT deficiency and abnormally low (<20 µmol/L) alpha-1 antitrypsin levels or there is a demonstrated family history of AAT deficiency, requested by a specialist or consultant physician. Where the result after genotyping is inconclusive, sequencing of the SERPINA1 gene to identify an AAT pathogenic variant should be conducted.

Type: Investigative

Medical condition this application addresses

Alpha-1 antitrypsin (AAT) is a serine protease inhibitor (serpin) synthesised and secreted mainly by hepatocytes. The primary function of AAT is to protect lung tissue damage caused by proteolytic enzymes, such as neutrophil elastase, that are generated to attack inhaled pollutants/pathogens. The AAT protein is encoded by the SERPINA1 gene, which expresses codominant alleles. Alpha-1 antitrypsin deficiency is a rare autosomal hereditary condition that results in decreased levels of circulating AAT, which then affects the lungs, liver, and sometimes, though rarely, the skin (e.g. necrotising panniculitis and vasculitis). In the lungs, AAT deficiency causes chronic obstructive pulmonary disease (i.e. emphysema, persistent airflow obstruction, and/or chronic bronchitis) at a young age. Individuals with phenotypes associated with plasma AAT levels below the protective threshold of 11 µmol/L are considered to have severe deficiency of AAT and are at elevated risk for emphysema. The most common mutations are PI*Z (Glu342Lys) and PI*S (Glu264Val); however, there are more than 100 genetic variants of the SERPINA1 gene, most of which are rare and only some are associated with clinical disease. A definitive diagnosis is of great importance in patients who might otherwise be misdiagnosed or missed altogether, allowing for earlier disease management, including preventive measures such as smoking cessation or prevention, and avoidance of exposure to environmental pollutants. 

Meetings to consider this application

  • PASC meeting: 13 August 2020
  • ESC meeting: 10 to 11 June 2021
  • MSAC meeting: 29 to 30 July 2021