1531 – Genetic testing of alpha thalassaemia

New MBS item

The proposed test is genetic testing for alpha thalassaemia common deletions by gap-PCR or multiplex probe ligation-dependent amplification (MLPA). Deletion testing is already performed in Australia, through state, grant or private funding or a combination of these, but varies between states and territories. The proposal is that deletion testing for alpha thalassaemia be supported by commonwealth funding. There are seven common deletions that cause the most serious forms of alpha thalassaemia, and deletion testing for these can be performed relatively easily using laboratory gap-PCR kits which include multiple probe sets, or using a step wise PCR regimen that is dependent on the patient’s racial background. Four of the most important deletions are named for their discovery within the populations of specific regions or countries (South East Asia, Mediterranean, Philippines and Thailand), and three others are named for the size of the deletion (20.7, 4.2 and 3.7 kilobases).

Type: Investigative

The thalassaemias are relatively common autosomal recessive disorders; the primary ones classified as either alpha or beta (other forms also exist), depending on which globin genes are affected. Functional copies of both alpha and beta globin chains are required for normal haemoglobin function. There are two alpha thalassaemia genes (alpha1 and alpha2) that lie adjacent to each other on chromosome 16, with every individual normally having four genes. These can carry point mutations, deletions or insertions deleterious to the gene function. A carrier may harbor a single mutation and show no disease impact, but two or more affected genes lead to a disease state ranging from mild microcytic anaemia to severe forms. In its most severe form, there will be little or no normal haemoglobin function, leading to Bart’s hydrops syndrome (usually no functional alpha genes), a condition that causes stillbirth or death of a child at birth, and is a known cause of maternal mortality. Haemoglobin H disease (HbH) is an important form of alpha thalassaemia and is varied in its presentation. HbH usually results from three gene deletions, including cis mutations (adjacent on the same chromosome). HbH may be asymptomatic but can result in moderately severe chronic haemolytic anaemia, which can be exacerbated by infection or other oxidative stress.

• PASC meeting: -
• ESC meeting: 8 February 2019
• MSAC meeting: 28 to 29 March 2019