Gene-based screening using GAP-PCR and MALDI-TOF MS versus haemogram-based screening for thalassaemia in early...

Thalassaemia is a common inherited disorder in Southeast Asia, including Vietnam. Conventional haemogram-based screening is widely used in routine prenatal care but has limited specificity and may be confounded by other conditions. This study compared gene-based screening using gap polymerase chain reaction (GAP-PCR) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) with haematologic indices for thalassaemia carrier detection in early pregnancy.

A prospective diagnostic accuracy study was conducted amongst 572 first-trimester pregnant women at Hanoi Obstetrics and Gynecology Hospital. All participants underwent both haemogram-based screening (defined as positive when mean corpuscular volume (MCV) <80 fL or mean corpuscular haemoglobin (MCH) <28 pg) and gene-based screening for 24 common α- and β-thalassaemia mutations using GAP-PCR combined with MALDI-TOF MS. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were compared.

Gene testing identified 101 carriers (17.7%): 64 α-thalassaemia (11.2%), 34 β-thalassaemia (5.9%), and 3 combined (0.5%). The predominant mutations were -SEA deletion (46.3% of α-thalassaemia) and HbE variant (48.6% of β-thalassaemia). Haematologic screening flagged 203 suspected cases (35.5%). Sensitivity was 100% for β-thalassaemia and 90.6% for α-thalassaemia, with a specificity of 77.1% for both. Six genetic carriers (all α-thalassaemia) had normal haematologic indices. PPVs were low (≤25.1%), while NPVs exceeded 98.9%.

Gene-based screening enhances diagnostic accuracy and identifies silent carriers missed by haemogram-based methods. These findings suggest a potential role in antenatal screening in high-prevalence settings, although cost-effectiveness and feasibility require further evaluation.