Serum Soluble Transferrin Receptor Concentrations Are Elevated in Congolese Children with Glucose-6-Phosphate Dehydrogenase Variants, but Not Sickle Cell Variants or α-Thalassemia

Abstract

Anemia is common in Congolese children, and inherited blood disorders may be a contributing cause. The presence of sickle cell variants, X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency and α-thalassemia, has been previously reported. A- deficiency is characterized by the co-inheritance of 376 and 202 variants and is common in sub-Saharan Africa. We aimed to measure the associations between inherited blood disorders and hemoglobin, ferritin, and soluble transferrin receptor (sTfR) concentrations in Congolese children. Venous blood was collected from 744 children aged 6-59 mo from 2 provinces. We measured biomarkers of nutritional and inflammation status and malaria. Pyrosequencing was used to detect sickle cell variants. Polymerase chain reaction was used to detect variants and α-thalassemia deletions. Overall, 11% of children had a sickle cell variant, 19% of boys were A- hemizygotes, 12% and 10% of girls were A- hetero- or homozygotes, respectively, and 12% of children had α-thalassemia. Multivariable linear regression models (adjusted for age, province, altitude, malaria, and biomarkers of nutritional and inflammation status) showed that A- hemizygous boys and 376 homozygous girls had higher sTfR concentrations [geometric mean ratios (95% CIs): 1.20 (1.03, 1.39) and 1.25 (1.02, 1.53), respectively] than children with no variants. Hemoglobin and ferritin concentrations were not independently associated with any of the inherited blood disorder genotypes. We found that 2 variant genotypes were associated with elevated sTfR concentrations, which limits the accuracy of sTfR as a biomarker of iron status in this population.

APOL1 Renal Risk Variants and Sickle Cell Trait Associations With Reduced Kidney Function in a Large Congolese Population-Based Study

“…The overall prevalence of SCT was 3.8% in our cohort, and previous studies reported higher prevalence in West DRC provinces (Kongo-Central and Kinshasa, >15%), 23 , 40 hence calling for further large-scale genetic studies. In our cohort, we did not identify any individual carrying the HbSS genotype, confirming the high mortality associated with sickle cell disease in childhood.…”

An update on glucose-6-phosphate dehydrogenase deficiency in children from Brazzaville, Republic of Congo

“…This study shows that 13% of the children were carriers of the severe G6PD deficiency genotype (A− for males and A−A− for females). This finding is consistent with studies conducted in the other Central African countries where the prevalence of G6PD deficiency ranges from 9 to 22% [22–26]. Previous studies reported a higher G6PD deficiency prevalence (22%) in 1988 and 1998 among children with sickle cell anaemia in the current setting [27, 28].…”

Micronutrient intake and prevalence of micronutrient inadequacy among women (15-49 y) and children (6-59 mo) in South Kivu and Kongo Central, Democratic Republic of the Congo (DRC)

“…The rates of iron deficiency based on sTfR (sTfR >8.3 mg/L) more closely align with dietary intake results. However, we recently showed in this population that sTfR is a poor diagnostic indicator of iron deficiency in population due to the high prevelance of inherited blood disorders [7]. Indeed, over half of the children in this sample had inherited blood disorders, and the presence of these genetic variants were significantly associated with elevated sTfR concentrations but not ferrtitin or haemoglobin.…”

“…We are aware that there are other causes of anemia such as malaria, helminths infection, and the presence of genetic blood disorders [5][6][7]. Nevertheless, we were perplexed by the general lack of micronutrient deficiencies in this population and sought corroborating evidence from dietary intake information that was obtained from 24 hour recalls in the study group.…”