Routine molecular screening for common a-thalassaemia deletions is necessary as part of an antenatal screening programme

I read with interest the paper by Sorour et al. which described one-year experience of routine molecular screening for common β-thalassemia deletions as part of an antenatal screening programme. ¹ Of the 5092 women booked at the antenatal clinic in their report, 425 screened positive for β-thalassemia trait using mean corpuscular haemoglobin (MCH) <27 pg and the absence of ²-thalassemia. All 425 samples were analysed by multiplex polymerase chain reaction (PCR) for six deletions (-SEA, -MED, -Ð^20.5, -FIL, -Ð^3.7 -Ð^4.2 genotypes), and 130 (31%) were positive for α deletions, including 12 (2.8%) heterozygous for α⁰-thalassemia. The 12 patients underwent partner testing. No couple was detected at risk of homozygous α-thalassemia. The authors argued that routine molecular screening for all forms of α-thalassemia trait is unjustified in antenatal screening.

Actually, the strategy of antenatal screening mentioned in the above report is not a simple and cost-effective one. It is true that the detection of a-thalassaemia trait remains a problem because of the lack of a readily available screening test, and genotyping of α-globin gene is always needed for diagnostic confirmation. However, in our local practice in southern China, when women were screened positive for α-thalassemia at their presentation for prenatal care at our hospital, we usually do not perform immediately a PCR analysis to determine the α deletions. ² Instead, we invite their partners to be screened. If both partners of a couple were tested positive for α-thalassemia trait, a multiplex PCR is then required to detect the α⁰-thalassemia. Only pregnancies in which both parents had an α⁰-thalassemia trait (-SEA) are considered at-risk of a child with hydrops fetalis and need a prenatal diagnosis by either invasive testing or non-invasive investigation. In the condition where only one parent screens positive for ²-thalassemia and the other screens negative, the molecular analysis is not performed for them, because the couple have no chance to deliver an offspring with severe homozygous state. Because DNA study is relatively expensive, the economic saving could be significant during the antenatal screening programme.

There is another point to which the authors should pay attention. In their antenatal screening programme, they screened the pregnant women for α-thalassemia using a low MCH level and a normal or reduced haemoglobin A2 level. If the women were tested positive, they received a PCR diagnosis. Those who were confirmed to be α⁰-thalassemia trait underwent partner testing. The authors might have neglected the double-heterozygote state for α- and β-thalassemia. The chance of discovering co-existing α-thalassemia in a β-thalassemia carrier depends on the individual's ethnic background. This chance is, therefore, relatively high in south-east Asia where 4-20% of the population are α-thalassemia carriers.^3–5 It is well known that routine screening tests, such as mean cell volume and haemoglobin A2 level, cannot distinguish double heterozygotes for α- and β-thalassemia from the pure β-thalassemia heterozygotes. ⁶ DNA diagnosis is necessary for differentiation. The diagnosis of this double-heterozygote state is important for genetic counselling, since unlike the typical β-thalassemia carriers, these individuals will be at risk of having an offspring with homozygous α⁰-thalassemia if they have a partner who is also an α⁰-thalassemia heterozygote. So, the authors might have missed potential cases of α⁰-thalassemia trait in their screening programme because they had not taken those double heterozygotes into account.