I read with interest the paper ‘A new strategy for prenatal diagnosis of homozygous α0-thalassemia’ by Leung et al.1. The authors report their experience in non-invasive prenatal detection of Bart's disease at two hospitals in southern China. Their non-invasive approach was successful, with a sensitivity of 100% and specificity of 95.6%. All the affected pregnancies were diagnosed before 24 weeks' gestation.
α-thalassemia is common in southern China. The gene frequency of α0-thalassemia is 4.1% in Guangdong province2. In the past, the prenatal diagnosis of this disease was achieved only by an invasive approach. Since 1999 a non-invasive approach, in which serial ultrasound examinations are performed from 12 weeks' gestation, has been used to exclude an affected pregnancy by some groups such as Lam et al. in Hong Kong3. The work reported in the paper by Leung et al. was carried out at two centers, one at Tsan Yuk hospital in which Dr Lam has served, and the other one at the Maternal and Neonatal Hospital of Guangzhou (MNH) in mainland China. Of the total 832 at-risk pregnancies studied, 473 were recruited at MNH. These 473 pregnancies were at risk of fetal homozygous α0-thalassemia. However, I am confused by the studies at MNH. In the ‘subjects’ part, the authors said ‘DNA diagnosis of homozygous α0-thalassemia was not established at MNH at the time of the study, and so cordocentesis and hemoglobin analysis was the standard diagnostic method’. So I would be interested to know how these 473 couples were designated as at risk of fetal homozygous α0-thalassemia since DNA diagnosis of α0-thalassemia was not available at MNH. Had all these couples been affected by hydrops fetalis due to homozygous α0-thalassemia in their previous pregnancies? If not, what methods were used at MNH for prenatal screening for α-thalassemia? It is well known that three α-globin gene mutations (--SEA, -α3.7, -α4.2) are the most common types for α-thalassemia in southern China. How was α0-thalassemia (--SEA) differentiated from α+-thalassemia (-α3.7, -α4.2) without molecular analysis?