1628 – Alpha-1-Antitrypsin Genotyping

Page last updated: 14 May 2020

Application Detail

Description of Medical Service

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 Ámol/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.

Description of Medical Condition

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 Ámol/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

Reason for Application

New MBS item

Medical Service Type

Investigative

Previous Application Number/s

Not Applicable

Associated Documentation

Application Form

Application Form (PDF 1656 KB)
Application Form (Word 400 KB)

Consultation Survey

Consultation Survey (PDF 558 KB)
Consultation Survey (Word 70 KB)

PICO Confirmation

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Assessment Report

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Public Summary Document

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Meetings for this Application

PASC

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ESC

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MSAC

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