The impact of H63D HFE gene carriage on hemoglobin and iron status in children

Abstract

The molecular mechanism that regulates iron homeostasis is based on a network of signals, which reflect on the iron requirements of the body. Hereditary hemochromatosis is a heterogenic metabolic syndrome which is due to unchecked transfer of iron into the bloodstream and its toxic effects on parenchymatous organs. It is caused by the mutation of genes that encode proteins that help hepcidin to monitor serum iron. These proteins include the human hemochromatosis protein -HFE, transferrin-receptor 2, hemojuvelin in rare instances, and ferroportin. HFE-related hemochromatosis is the most frequent form of the disease. Interestingly, the low penetrance of polymorphic HFE genes results in rare clinical presentation of the disease, predominantly in middle-aged males. Taking into account the wide dispersion of HFE mutation in our population and also its unknown role in heterozygotes, we analyzed the impact of H63D HFE carriage in the developmental age, with respect to gender, on the iron status and hemoglobin concentration of carriers in comparison to those of wild-type HFE gene (12.7 ± 3.07 years, 42 boys and 41 girls). H63D carriers presented higher blood iron, transferrin saturation, and ferritin concentration than wild-type probands (p < 0.05.) Interestingly, male H63D carriers showed higher hemoglobin concentration than the unburdened children. Moreover, in the H63D carrier group, a positive correlation between iron and hemoglobin was noted. In conclusion, this study demonstrates that changes in iron metabolism occur at a young age in HFE heterozygotes.

The association of HFE gene H63D polymorphism with endurance athlete status and aerobic capacity: novel findings and a meta-analysis

“…Individuals with one (C/G or H63D genotype) or two (G/G or D63D genotype) missense mutations of the H63D (also known as His63Asp or rs1799945 C/G) polymorphism, show higher circulating iron concentrations than people without mutations (Burt et al 1998). In the H63D carrier group, a positive correlation between iron and hemoglobin was noted (Barbara et al 2016). The H63D mutation is commonly found in European (17%) and American (12%) populations, and is rarer in East Asian (3%), South Asian (7%), and African (1%) populations.…”

Reduction of Skeletal Muscle Power in Adolescent Males Carrying H63D Mutation in theHFEGene

“…The H63D mutation of HFE gene is cosmopolitan but greater in white populations (10% to 29%) of western Europe [ 6 ], whereas H63D simple heterozygosity is more prevalent (23.6% to 31.1%) in populations of northern European and our population [ 30 , 31 ]. Despite these high prevalence and association with the risk of iron overload the population of HFE H63D heterozygotes has not been widely examined, especially in children.…”

“…Furthermore the intensity of iron storage and influence on physical performance in HFE carriers in the developmental age are not well elucidated. Notably, since iron accumulation is a prolonged process, iron overload is rarely observed in children [ 30 ]. Thus early diagnosis, monitoring, and treatment are essential.…”

Exome sequencing for diagnosis of congenital hemolytic anemia

“…P33 harbored G6PD and SPTB variations, which combination cannot explain the severe phenotype. P34 had UH and iron overload, and variations in 3 genes: a homozygous p.H63D variation in HFE, which may contribute to iron overload even though its implication is not totally clear [55,56], a heterozygous ABCG8 VUS and 2 heterozygous ADAMTS13 VUS. ABCG8 mutations are found in AR sitosterolemia and AD xanthelasma [57].…”