α:Non-α and Gγ:Aγ globin chain ratios in thalassemia intermedia patients treated with hydroxyurea

Objectives: To elucidate the possible ways by which hydroxyurea molecules affect globin chain (α or β-like) synthesis. Methods: A total of 23 thalassemia intermedia patients (13 male and 10 female) aged between 5 and 26 years were treated for five months with 15 mg/(kg-day) of hydroxyurea. Hemoglobins electrophoresis and globin chain electrophoresis was performed on each sample at different time points before and during the treatment. Results: Fetal hemoglobin increased significantly in most patients and average episodes of transfusion decreased. Both Gγ and Aγ-globin chains increased significantly and α-globin:Nonα-globin chain as well as Gγ-globin:Aγ globin chains ratios decreased. Conclusions: Improvement in α:non-α ratio and consequent decrease of free α-globin chain might be the cause of beneficial effects of hydroxyurea therapy. Two patients who felt better didn't show significant increase in their fetal hemoglobin level, and this is in contradiction with the hypothesis claiming that the HbF level increase is the cause of such therapeutic effect. In spite of the unclear mechanism of action of this drug, hydroxyurea therapy had noticeable impacts on thalassemia intermedia and also sickle cell disease and even patients suffering from thalassemia major. © 2014 by the Asian Pacific Journal of Tropical Biomedicine

Relation between neonatal icter and gilbert syndrome in gloucose-6-phosphate dehydrogenase deficient subjects

Background and Aim: The pathogenesis of neonatal hyperbilirubinemia hasn't been completely defined in Gloucose-6-Phosphate Dehydrogenase (G6PD) deficient newborns. The aim of this study was to detect the relationship between Gilbert's syndrome and hyperbilirubinemia in Gloucose-6-Phosphate Dehydrogenase (G6PD) deficient neonates. Materials and Methods: This case-control study was conducted in Amirkola pediatrics teaching hospital, Babol, Iran. A total number of one hundred four infants were included in the study (51 infants with neonatal jaundice and Gloucose-6-Phosphate Dehydrogenase (G6PD) deficiency admitted to phototherapy or transfusion were selected as the case group and 53 infants with Gloucose-6-Phosphate Dehydrogenase (G6PD) deficiency admitted for other reasons than jaundice were selected as the control group). Exclusion criteria were ABO or Rh incompatibility or other reasons that made Coombs test positive, sepsis, hepatosplenomegaly, metabolic diseases, medical treatment and phototherapy. The promoter and coding regions of Uridine diphosphate Glucuronosyl Transferase 1A1 (UGT1A1) of genomic DNA were amplified by polymerase chain reaction (PCR) isolated from leukocytes. We used chi-square test and t-test to compare cases and controls. Results: Distribution of Gilbert genome was not significantly different between the two groups; among cases, 33.3% were homozygote, 35.3% heterozygote, and 31.4% normal. Among controls, 22.6% were homozygote, 34% heterozygote, and 43.4% normal (p-value=xxx). Hyperbilirubinemia family history didn't differ significantly between these two groups. Conclusions: We showed that in Gloucose-6-Phosphate Dehydrogenase (G6PD) deficient neonates, there was no significant association between Gilbert's syndrome (promoter polymorphism) and hyperbilirubinemia

The association between prolonged jaundice and TATA box dinucleotide repeats in Gilbert’s syndrome

Introduction: Jaundice is a common condition during the neonatal period. Prolonged jaundice occurs in a large number of breastfed infants, considering the impact of genetic factors on the incidence of jaundice. Aim: To determine the association between prolonged jaundice and TATA box dinucleotide repeats in Gilbert’s Syndrome (GS). Materials and Methods: In this case-control study, the case group consisted of 51 neonates with jaundice, aged more than two weeks with indirect bilirubin level higher than 10 mg/dl. Acute diseases, mother’s use of phenobarbital and other medications were the exclusion criteria. The control group consisted of 54 newborns without jaundice. The two groups were matched in terms of age and sex. TATA box polymorphisms in the promoter region of UGT1A1 gene were evaluated using Polymerase Chain Reaction (PCR) in order to determine TATA box dinucleotide repeats. Results: Overall, 64.7 and 50 of subjects in the case and control groups were male, respectively (p=0.168). The mean age of neonates in the case and control groups was 20.1±7.1days and 18.8±4.1 days, respectively. The distribution of Gilbert genome was not significantly different between the two groups. In the case group, 13.7 of the subjects were homozygous, 37.3 were heterozygous and 49 were normal. In the control group, 7.4 of the participants were homozygous, 35.2 were heterozygous and 57.4 were normal. Conclusion: The results of this study showed an association between TATA box polymorphism and prolonged jaundice in neonates which revealed that TATA box polymorphism is an important risk to increase and extend icterus. © 2017, Journal of Clinical and Diagnostic Research. All rights reserved