Serum hepcidin level and disease course of acute leukemia in children

Acute leukemia [AL] is a heterogeneous group of hematopoietic neoplasms and it is the most common childhood malignancy. Many patients with AL develop severe anemia that requires multiple blood transfusions. Hepcidin expression may play a role in anemia which is often seen in these patients. The aim of this study is to evaluate the role of hepcidin in acute lymphoblastic leukemia in children in Egypt. 60 patients with acute lymphoblastic leukemia [ALL] and 20 age and gender matched healthy children, taken as control group, were included in the study. Complete blood count [CBC], Serum ALT and serum AST were measured by colorimetric methods. Serum hepcidin and ferritin were measured by ELISA. The study showed a significant difference between newly diagnosed ALL cases and other groups regarding all CBC parameters. There was a significant difference in serum levels of hepcidin and ferritin between studied groups. A significant negative correlation was found between serum level of hepcidin and ferritin and each of hemoglobin level and reticulocytic count%, while significant positive correlation was found between hepcidin and ferritin serum levels. From this study, it could be concluded that serum hepcidin level is elevated in ALL children patients at time of diagnosis and correlates with the disease extent. Hepcidin may be one of the serum markers that accounting for anemia associated with ALL in children

L-Carnitine ameliorates the iron mediated DNA degradation in peripheral leukocytes of beta-thalassemic children

Iron overload is a common complication in beta-thalassemia that induces intracellular oxidative stress producing lesions in the DNA including double strand breaks. The aim of this study was to evaluate DNA damage in peripheral leukocytes of-thalassemic children and to investigate its association with the iron overload and the role of L-carnitine therapy upon this damage. Fifty beta-thalassemic children [25 TM and 25 TI] with 20 age and sex matched apparently healthy children [control group] were included. Serum ferritin level was measured by ELISA. DNA damage was evaluated by the Gel electrophoresis to determine the total DNA genomic damage [TGD]. The intensity of DNA nucleoprotein was measured by software Gel Pro analyzer computer program as maximum optical density [max.OD] values of apoptotic fragments of DNA at 200bp, 400bp and 600bp. The smear shape pattern on gel electrophoresis and Pro-Gel analyzer chart indicating double strand breakage of the DNA was detected in 76% of the thalassemic children. The thlassemic patients [the whole group and each of TM and TI groups] had significantly higher prevalence of DNA double-strand breaks in their leukocytes with significant higher values of max. OD at 200,400and 600 bp compared to the control group. The thalassemic children on regular L-carnitine therapy [50 mg/kg/d for at least 6 months] had significantly lower prevalence and degrees of DNA breaks [TGD] with significant lower max. OD values at 200,400 and 600 bp compared to those not on L-carnitin therapy. There was significant positive correlation between the mean serum ferritin levels and the values of max. OD at 200 and 400bp. The data obtained from the Roe Curve shows that, the best sensitivity of 95% and specificity of 75% for the mean serum ferritin were at the cut off point of 820 ng/ml to predict the ocurrence of TGD in thalassemic leukocytes. Thalassemic children had significant DNA double-strand breaks in their leukocytes that was positively correlated to their iron overload reflected by serum ferritin level and can be ameliorated by L-carnitine supplementation

Haemochromatosis gene mutation H63D is a risk factor for iron overload in Egyptian beta- thalassemic children

Iron overload is the main cause of morbidity and mortality in patients with beta-thalassemia. The aim of this study was to evaluate the prevalence of genetic markers [HFE mutations C282Y and H63D] among Egyptian beta-thalassemic Children and its effect on their iron status. 59 beta-thalassemic children attending the pediatric hematology clinic in Menoufiya University Hospital [23 thalassemia major, 23 thalassemia intermedia and13 thalassemia trait] with 50 apparently healthy, Egyptian children [control group] were screened for the prevalence of these two mutations by digestion of PCR products [RFLP]. Serum ferritin level was measured by ELISA. Neither carrier status for the C282Y allele nor homozygous status for the H63D allele were detected in any of the thalassemic children or the 50 controls. The H63D heterozygous state was detected in 15 [25.4%] thalassemic patients with an allele frequency of 12.71% and in 11 [22%] controls with an allele frequency of 11%. with no significant difference between the thalassemic groups and the controls. The prevalence of carriers for the H63D mutation was 26.1% with an allele frequency of 13.04% in patients with either beta- thalassemia major or intermedia, while in beta- thalassemia trait the prevalence of this mutation was 23.1% with an allele frequency of 11.54%. There were significant higher levels of the mean yearly serum ferritin in both beta-thalassemia major and intermedia patients who are heterozygotes for the H63D mutation compared to those without this mutation. The mean serum ferritin levels were positively correlated with the age of the patients. On the other hand, the prevalence of iron -induced complications was not statistically different between patients carrying or not carrying this mutation [among TM and TI]. There is no difference in the prevalence of H63D mutation between beta-thalassemic patients and the normal children and the presence of a heterozygous H63D status and older age are two risk factors for iron overload in Egyptian beta-thalassemic children. RFLP= Restriction Fragment Length Polymorphism, HCV=Hepatitis C Virus, ALT = Alanine aminotransferase, AST =Aspartate aminotransferase