Safia K Ali, Elshazali W Ali
The frequency of the HFE gene H63D mutation was relatively high among Sudanese children with βTM, whereas the S65C variant was absent. Although SF levels were higher in the carriers of the H63D variant allele compared to those with the wild-type allele, the difference was not statistically significant. These findings indicate limited clinical utility for routine screening for the HFE H63D and S65C mutations and emphasize the greater importance of optimizing transfusion and iron-chelating therapy practices to manage IO effectively.
INTRODUCTION: Coinheritance of HFE gene mutations in patients with β-thalassemia major (βTM) may further exacerbate systemic iron accumulation, potentially leading to earlier onset of iron-related complications. This study aimed to screen for HFE gene H63D and S65C mutations in children with βTM and evaluate their impact on the severity of secondary iron overload (IO).
MATERIALS AND METHODS: This cross-sectional study included 76 Sudanese children with βTM who were all receiving regular blood transfusions and iron chelation therapy. Polymerase chain reaction and Sanger DNA sequencing were used to screen for H63D and S65C mutations. IO severity was assessed by measuring serum ferritin (SF) levels using electrochemiluminescence immunoassay.
RESULTS: The H63D mutation was identified in 17 (22.4%) of the thalassemic children; 16 (21.1%) were heterozygous, and one (1.3%) was homozygous. The S65C mutation was not present in any of the participants. SF levels were higher among carriers of the H63D variant allele (CG + GG) than among those with the wild-type allele (CC). Still, the difference was not statistically significant (median: 2051.0 vs. 1460.0 μg/L, p = 0.09). Furthermore, no statistically significant association was observed between the H63D mutation and the risk of myocardial iron loading (p = 0.087). The results revealed a statistically significant positive correlation between SF levels and the total number of blood transfusions (Spearman's ρ = 0.496, p < 0.001). A weak, positive, insignificant correlation was observed between SF levels and both the time since the last dose of iron chelation therapy (ρ = 0.257, p = 0.100) and C-reactive protein levels (ρ = 0.129, p = 0.267).
CONCLUSIONS: The frequency of the HFE gene H63D mutation was relatively high among Sudanese children with βTM, whereas the S65C variant was absent. Although SF levels were higher in the carriers of the H63D variant allele compared to those with the wild-type allele, the difference was not statistically significant. These findings indicate limited clinical utility for routine screening for the HFE H63D and S65C mutations and emphasize the greater importance of optimizing transfusion and iron-chelating therapy practices to manage IO effectively.