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Background Thalassaemia is a haemoglobin disorder caused by a reduction in, or a complete absence of, the production of α- or β-globin genes. Detection of β-thalassaemia carriers is the first step in the prenatal diagnosis of the disease and is based primarily on the differences between levels of blood cell indices. Since co-inheritance of β- and α-thalassaemia mutations modulates the haematological parameters of heterozygote β-thalassaemia indices, understanding the influence of this interaction is helpful for identification of disease carriers. Objective To determine the effects of α-thalassaemia mutations on the haematological parameters of β-thalassaemia carriers. Method We used gap-PCR and amplification refractory mutation system techniques to find any α- and/or β-thalassaemia mutations in 270 subjects who were suspected to be thalassaemia carriers. The mean values of the haematological parameters in α, β-thalassaemia and β-thalassaemia carriers were compared. Results Significant differences in mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and HbA2 were found between the two groups. Patients who were α, β-thalassaemia carriers had higher mean values of MCV and MCH, whereas HbA2 levels were higher in simple β-thalassaemia. No marked differences were found in mean cell haemoglobin (Hb) concentration and Hb blood cell indices. The value of MCV, MCH and HbA2 were significantly different between α,β-thalassaemia and simple β-thalassaemia in men and women, but the mean values of Hb in the two groups differed markedly only in men. Conclusion We conclude that co-inheritance of α- and β-thalassaemia mutations may result in misdiagnosis of β-thalassaemia carriers. Therefore, in genetic counselling of patients with a near-normal range of blood cell indices the possibility that they may carry α, β-thalassaemia mutations must be considered.

OBJECTIVE To compare red blood cell hematology among fetuses at risk of homozygous β-thalassemia disease at mid-pregnancy. MATERIALS AND METHODS Eighty-six fetuses, 18 to 22 gestational weeks, at risk of homozygous β-thalassemia disease undergoing cordocentesis between December 2010 and June 2012 were recruited in the study. Red blood cell parameters were measured and final diagnosis of thalassemia status was based on fetal hemoglobin typing by high performance liquid chromatography technique and DNA analysis. The fetuses were categorized into 3 groups as normal β-globin genotype, β-thalassemia trait, and homozygous β-thalassemia disease. RESULTS Mean maternal age and mean gestational age were 26.56±6.36 and 19.12±1.06 weeks, respectively. The prevalence of fetuses with homozygous β-thalassemia disease, β-thalassemia trait, and normal β-globin genotype fetuses were 29.07% (25 cases), 20.93% (18 cases), and 50% (43 cases), respectively. All of red blood cell parameters were not significantly different among the 3 groups of fetuses. No affected fetus had anemia during mid-pregnancy. CONCLUSION No significant difference in red blood cell parameters among unaffected and affected fetuses with homozygous β-thalassemia disease was found.

Currently, amniocentesis, chorionic villus sampling (CVS) and fetal blood sampling are used to obtain fetal cells for genetic diagnosis. These invasive procedures pose a small but not negligible risk for the fetus. Efforts have been directed towards the enrichment of fetal cells, such as erythroblasts, from maternal blood and progress has been made in the diagnosis of some chromosomal disorders and in sex determinations. We now report the detection of point mutations in single gene disorders using this method of prenatal diagnosis by enriching fetal cells from maternal blood by magnetic cell sorting followed by isolation of pure fetal cells by microdissection. In two pregnancies at risk for sickle cell anaemia and beta-thalassaemia, we successfully identified the fetal genotypes. Thus, prenatal diagnosis of single gene disorders by recovering fetal cells from maternal circulation appears to be a feasible approach.

Introduction This resource is a problem-based learning (PBL) case on alpha-thalassaemia syndrome (i.e., patient with Hemoglobin H disease). At our university, medical genetics is taught in first and second semester, so this version of the case most naturally is directed at first-year medical students in a similar program. However, the case can easily be altered to involve more pathology for use in medical schools that teach genetics during the second year. Methods The case naturally leads the students to study causes of fatigue and then anemia, especially microcytic anemia. Students then compare and contrast thalassaemia with iron deficiency anemia. This PBL case involves three sessions. Students are presented with the first five pages of the case in session one. After students learn and discuss the research in session two, the students are presented with additional notes. Finally during session three the postscript and expected learning issues are handed out. As our expectation is that no facilitator can be an expert in all aspects of a case, a Faculty Notes file with background information is included. Results This case was developed during 2005 and has since been used in the author's PBL program once to twice a year. It has proven to be a well-functioning case which generally has been well received by facilitators and students alike. Discussion The case requires the students to interpret a hemoglobin electrophoresis pattern presented as an illustration. An expected learning issue involves the review of population incidence differences in the occurrence of hemoglobinopathies. Appropriate genetic counseling is most often also researched.

This 22-year-old women presented to the ante-natal clinic of this hospital for prenatal screening for beta-thalassemia. Cation exchange high performance liquid chromatography (HPLC) using 'Beta Thalassemia Short Program' on Bio-Rad 'Variant' system revealed HbC value of 81.6%. The CBC showed microcytic hypochromic anemia. The HPLC and CBC suggested the possibility of compound heterozygote state for HbC/beta-thalassemia. The alkali and acid electrophoresis findings were consistent with the above diagnosis. The DNA analysis confirmed compound heterozygote state for HbC/beta(0)-thalassemia (Fr 8/9 mutation). The studies on the parents showed that mother was a compound heterozygote for HbD(Punjab) and HbC while father had beta-thalassemia trait. To the best of our knowledge, this is the first confirmed report of HbC from India. The paper discusses the hematological findings in this subject and her mother (a compound heterozygote for HbD(Punjab) and HbC).

Fetal nucleated red blood cells (NRBCs) entering maternal circulation during pregnancy constitute a potential source of material for safe and reliable noninvasive prenatal diagnosis. The increased prevalence of beta-thalassemia mutations in countries like Greece may create a problem, making it difficult to distinguish between NRBCs of fetal or maternal origin. Use of Ab against embryonic hemoglobin epsilon may increase specificity for fetal NRBC detection. In the present study, Ab against embryonic hemoglobin epsilon was used in the first and second trimesters of pregnancy in order to determine if specificity for fetal NRBC detection could be increased.