Variable haematological and clinical presentation of ß-thalassaemia carriers and homozygotes with the Poly A (T→C) mutation in the Indian population.

OBJECTIVES: To study the varied clinical and haematological profile of ß-thalassaemia homozygotes, compound heterozygotes and heterozygotes with the Poly A (T→C) mutation and its implication in prenatal diagnosis. MATERIALS AND METHODS: Forty individuals were included in the study. Peripheral smear examination, complete blood count and haemoglobin analysis were carried out. ß-thalassaemia mutation analysis was carried out by reverse-dot-blot hybridization, amplification refractory mutation system and DNA sequencing of the ß-globin gene. RESULTS: Five of the six ß-thalassaemia homozygotes with the Poly A (T→C) mutation and five individuals who were compound heterozygous for the Poly A (T→C) mutation along with another common Indian ß-thalassaemia mutation showed a severe ß-thalassaemia major phenotype, while one individual presented as a thalassaemia intermedia. Majority of the 28 heterozygous individuals with this mutation showed borderline HbA2 (mean HbA2 = 3.7 ± 0.4%) levels as compared to individuals with common ß-thalassaemia mutations (mean HbA2 = 5.2 ± 1.4%). The Mean Corpuscular Volume (MCV) levels in individuals heterozygous for the Poly A (T→C) mutation (mean MCV 70.0 ± 5.2 fl) were significantly higher than in individuals with other common ß-thalassaemia mutations (mean MCV 60.7 ± 7.7 fl) (P < 0.001). CONCLUSION: It is important to identify these often silent carriers of ß-thalassaemia for prenatal diagnosis as homozygotes have a severe disease.

Molecular characterization of delta beta-thalassemia and hereditary persistence of fetal hemoglobin in the Indian population.

delta beta-Thalassemia (delta beta-thal) and hereditary persistence of fetal hemoglobin (HPFH) are heterogeneous disorders characterized by elevated levels of Hb F in adult life. The two disorders should not be considered as unambiguously separate entities but rather as a group of disorders with a variety of partially overlapping phenotypes. This study was undertaken to determine the hematological and molecular characteristics of high Hb F determinants among Indians. A gap-polymerase chain reaction (gap-PCR)-based approach was used for molecular characterization of high Hb F phenotypes. Fifty-five unrelated individuals were studied. The molecular findings were correlated with the hematological data. DNA analysis identified the deletion-inversion (G)gamma((A)gamma delta beta)(0)-thal in 15 cases (27%) and the HPFH-3 (Indian deletion) determinant in 26 cases (47.2%) and the Vietnamese/Chinese determinant (27 kb deletion) in five cases (9%), which is being reported for the first time from India; 16% (nine cases) of the samples remained uncharacterized. This study emphasizes that delta beta-thal and HPFH determinants are common in India. Molecular analysis will aid in understanding genotype-phenotype correlations and will facilitate prevention and control programs of thalassemia and hemoglobinopathies in this region.

Carrier screening for beta-thalassemia during pregnancy in India: a 7-year evaluation.

AIM: Premarital screening for beta-thalassemia is not widely acceptable in India; hence, we evaluated the effectiveness of antenatal screening and counseling over 7 years. METHODS: 61,935 pregnant women were screened using the single-tube osmotic fragility test during their first antenatal visit. Individuals who were positive were investigated further for diagnosis of beta-thalassemia and other abnormal hemoglobins. Spouses of carrier women were tested whenever available. Couples at risk were given the option of prenatal diagnosis. RESULTS: Only 19% of the women registered at the antenatal clinic in the first trimester of pregnancy, and 14% of the women were positive per the osmotic fragility test; 1020 beta-thalassemia heterozygotes and 213 women with other hemoglobinopathies were identified, majority being in the second and third trimesters. Seven hundred and thirteen (69%) of their husbands could be tested, and 37 couples at risk were identified. Only 15 couples had a prenatal diagnosis done. Four couples with affected fetuses opted for termination of pregnancy. The remaining couples either did not respond after counseling or the pregnancies were advanced for prenatal intervention. CONCLUSION: This first large study shows that antenatal screening is acceptable in India; however, awareness generation is still a primary requisite to make women register early at antenatal clinics and bring their spouses for screening when required.