In β-thalassemia, certain mutations cause a complete absence of β-globin chain synthesis, termed β-thalassemia, while others may allow certain β-globin production and are termed β- or β-thalassemia. The homozygous state results in severe anemia, which requires regular blood transfusion. By contrast, frequent blood transfusion can in turn lead to iron overload, which may result in several endocrinal complications. The present study aimed to investigate the impact of genotype on the development of endocrine complications in β-thalassemia patients. A cross-sectional study was conducted on 100 thalassemia patients >10 years. A data abstraction form was designed to capture the appropriate information from the individual medical records, including full clinical, laboratory, transfusion and chelation data. The genotype of the patients was identified by the DNA sequencing technique. Growth retardation and hypogonadism were the most prominent endocrinal complications (70 and 67%, respectively) followed by hypothyroidism, diabetes mellitus and hypoparathyrodism (8, 8 and 7%, respectively). The most common mutations identified were IVS-1-110, IVS-1-1 and IVS-1-6 (63, 47 and 41%, respectively). Patients with the ββ genotype had a significantly higher prevalence of growth retardation, hypogonadism, hypothyroidism and hypoparathyrodism compared to those with the ββ and ββ genotypes (P<0.001, P<0.001, P<0.001 and P=0.037, respectively). Patients with the homozygous IVS-11-745 mutation had a significantly higher prevalence of diabetes (P=0.001). The underlying genetic defect in thalassemia patients is a contributing factor for the development of endocrinal complications, as patients with the more severe defects have a greater rate of iron loading through higher red cell consumption.

BackgroundThe study aimed to gain first data on the prevalence of G6PD enzyme deficiency measured by spectrophotometry and associated genetic variants in Jimma and surroundings, Ethiopia. The area is a Plasmodium vivax endemic region, but 8-aminoquinolines such as primaquine are not recommended as G6PD testing is not available.MethodsHealthy volunteers were recruited at Jimma University, Ethiopia. Enzyme activity was tested by spectrophotometry at the University of Ulm, Germany. A G6PD RDT (Binax NOW® G6PD, Alere, USA) was additionally performed. The G6PD gene was analysed for polymorphisms in a sub-population. Tests for haemoglobinopathies and the presence of malaria parasites were conducted.ResultsNo severe or moderate (cut-off 60%) G6PD deficiency was found in 206 volunteers. Median male activity was 6.1 U/g Hb. Eleven participants (5.4%) showed activities between 70 and 80%. No haemoglobinopathy was detected. None of the subjects showed asymptomatic parasitaemia. One G6PD-A+ variant (A376G) and one new non-synonymous mutation (G445A) were found.ConclusionsAs the prevalence of G6PD deficiency seems low in this area, the use of 8-aminoquinolines should be encouraged. However, reliable G6PD testing methods have to be implemented and safe cut-off levels need to be defined.Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2510-3) contains supplementary material, which is available to authorized users.

Codon 104(-G), a dominant β -thalassemia-like phenotype in a German Caucasian family is associated with mild chronic hemolytic anemia but influenced in severity by co-inherited genetic factorsCodon 104(-G), a heterozygous frameshift mutation in exon 2 of HBB, resulted in a dominantly inherited β 0 -phenotype with mild anemia in a German kindred, and thalassemia intermedia in the index patient. A co-inherited α gene triplication, long-term transfusion therapy, and ineffective erythropoiesis were confounding factors. Haematologica 2007; 92:1264 92: -1265 We report a β 0 -thalassemia deletion mutation with dominant mode of inheritance in a German Caucasian family of Huguenot descent (Figure 1). The proposita (IV-5) presented in our hospital (2002) with hepatosplenomegaly and a Thalassemia intermedia phenotype. Erythrocytes had been previously transfused to her (300 units) and her brother (IV-2, 500 units). Her brother died of malignant melanoma in 2003. Transfusion therapy was continued in the proposita up to the time, when iron overload became evident. From 1999, she had been treated with erythropoietin and iron chelation therapy. Her sister (IV-7) and daughter (V-4) presented with mild chronic hemolytic anemia. Elevated HbA2 (3.9-5.1%) and HbF-levels (3.8 and 5.1%) in the proposita and her daughter (V-4) were detected by high performance liquid chromatography on an ÄKTA Tm basic 10A system (Amersham Biosciences, Freiburg). Low values for Hb (7.7-11.2 g/dL), Hct (28-35%), MCV (69-73.2 fl) and MCH (22.1-24.2 pg) indicated hypochromic anemia (Table 1). Erythrocyte enzyme activities for glycolysis and pentose phosphate cycle were normal. Elevated serum concentrations of iron (39.3 µmol/L), ferritin (2016 µg/L) and a transferrin saturation of 89.8% denoted iron overload and/or hemochromatosis in the proposita. Ultrasonography and computerized tomography showed increased hepatic density, a clinical sign of iron overload. The absence of aberrant or unstable hemoglobin fraction in biochemical Hb analyses together with a thalassemia-like clinical picture suggested β 0 -thalassemia. Informed consent was given for genetic analyses. DNA extraction and polymerase chain reaction (PCR) analysis were performed using standard methods, sequencing with a CEQ Quick Start Kit on a CEQ 8800 automated DNA Sequencer (Beckman Coulter, Krefeld). Primers and PCR conditions are available from the authors upon request. The family members were heterozygous for a β-thalassemia mutation [codon 104 (-G)] at the exon2/IVS-II boundary within a homonucleotide run of three guanines (494-496; -G) ( Figure 2A). The deletion mutant at the end of Figure 1. Pedigree of German kindred shows segregation of dominantly transmitted β β-Thalassemia. The proposita is marked by an arrow; : dead; : dominant Thalassemia; : healthy; : heterozygous; ?: unconfirmed disease. Table 1. Hematological data of four members of German index family (after discontinued transfusion therapy of members IV-2 and IV-5). -1925- F-1933- F-1938- F-1963 94 Both mutation-dependen...

Background Inherited blood disorders affect 7% of the population worldwide, with higher prevalences in countries in the “thalassemia belt,” which includes Bangladesh. Clinical management options for severely affected individuals are expensive; thus, targeted government policies are needed to support prevention and treatment programs. In Bangladesh, there is a lack of data, in particular community-based estimates, to determine population prevalence. This study aims to estimate the prevalence of a wide range of hemoglobinopathies and their associations with anemia in a community-based sample of women and young children in rural Sylhet, Bangladesh. Methods Capillary blood samples from 900 reproductive-aged women and 395 children (aged 6–37 months) participating in the Food and Agricultural Approaches to Reducing Malnutrition (FAARM) trial in two sub-districts of Habiganj, Sylhet Division, Bangladesh were analyzed for alpha thalassemia, beta thalassemia, and other hemoglobinopathies. We examined the association of each inherited blood disorder with hemoglobin concentration and anemia using linear and logistic regression. Results We identified at least one inherited blood disorder in 11% of women and 10% of children. Alpha thalassemia was most prevalent, identified in 7% of women and 5% of children, followed by beta thalassemia and hemoglobin E in 2–3%. We also identified cases of hemoglobin S and hemoglobin D in this population. Having any of the identified inherited blood disorders was associated with lower hemoglobin values among non-pregnant women, largely driven by alpha and beta thalassemia. Pregnant women with beta thalassemia were also more likely to have lower hemoglobin concentrations. Among children, we found weak evidence for a relationship between hemoglobinopathy and lower hemoglobin concentrations. Conclusions We found a high prevalence of alpha thalassemia among both women and children in rural Sylhet, Bangladesh–higher than all other identified hemoglobinopathies combined. Community-based estimates of alpha thalassemia prevalence in Bangladesh are scarce, yet our findings suggest that alpha thalassemia may comprise the majority of inherited blood disorders in some regions of the country. We recommend that future research on inherited blood disorders in Bangladesh include estimates of alpha thalassemia in their reporting for public health awareness and to facilitate couples  counseling.

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