Age dependency of plasma vitamin B12 status markers in Dutch children and adolescents

Abstract

Background Vitamin B12 deficiency in children may be associated with (severe) neurological manifestations, therefore recognition is important. Diagnosing vitamin B12 deficiency in children is challenging. This study aimed to investigate plasma methylmalonic acid, holotranscobalamin, and total cobalamin in children 0–18 years of age and to estimate age-dependent reference intervals. Methods Plasma vitamin B12 markers were measured in collected plasma samples of 170 children 0–18 years visiting a local primary care laboratory. All had within-reference hemoglobin and MCV values. Pediatric plasma vitamin B12 biomarkers were measured and reference values were derived thereof. Results Plasma methylmalonic acid was higher in young children, in particular between 1 and 6 months of age; total cobalamin and holotranscobalamin were highest from 0.5 to 4 years and decreased till 10 years of age. Plasma holotranscobalamin was highly correlated with plasma total cobalamin; their ratio was independent of age. Plasma methylmalonic acid was slightly more related to total cobalamin than to holotranscobalamin. A large proportion of mainly young children would be misclassified when adult references are applied. Conclusions Pediatric reference values for cobalamin markers are necessary to allow for early recognition and monitoring of children suspect of (clinical) cobalamin deficiency. Impact We analyzed three plasma vitamin B12 status markers, i.e., total cobalamin, holotranscobalamin, and methylmalonic acid, in the plasma of 170 children 0–18 years of age and were able to derive reference intervals thereof. Recognition of vitamin B12 deficiency in children is important but challenging as pediatric reference intervals for plasma vitamin B12 status markers, particularly plasma holotranscobalamin, are not well described. We think that our results may help early recognition and monitoring of children suspect of (clinical) vitamin B12 deficiency.

Diagnosis of Vitamin B12 Deficiency in Children by Using Methylmalonic Acid, Homocysteine and Holotranscobalamine

“…Limitations of the study: There are not many studies in the literature about the relationship between holoTC, blood MMA and vitamin B12 and therefore cut-off values in children are not accurate (22). Unfortunately, we could not give a well-defined cut-off value for determining vitamin B12 deficiency since we did not have a control group.…”

Lack of Clinical Evidence Regarding the Guidelines for Vitamin B12 Deficiency: An Analysis From Literature and Recommendations From Clinical Practice

“…Other scientists repeat this research with similar outcomes as a result. 24 -28 Despite these differences, which can be well explained since cobalamin is not only involved in the production of red blood cells but is also essential for cell division and DNA (children are developing), existing guidelines do not address children with vitamin B12 deficiency. 21 This practice may lead to underdiagnosis and unnecessary suffering in children.…”

Vitamin B12 Deficiency in Children and Adolescents: A Case for Revised Diagnostic Parameters

“…Published studies from 2003 to recently highlight the significant variations in age-related B12 levels in healthy children compared with the diagnostic thresholds of adults. [14][15][16][17][18][19] With the caveat that some studies may have been conducted in children who attended the clinics for other conditions or underwent surgical procedures that may have affected the outcome of the blood values. Minor surgical procedures in children under nitrous oxide anesthesia, for example, can already influence the results in B12, methylmalonic acid (MMA), and homocysteine levels.…”

“…20,21 Current diagnostic criteria, aligned with those for adults, overlook substantial age-related variations in B12 levels observed in healthy young individuals. The average values for children aged 10 to 13 years are at least twice as high as for adults [14][15][16][17][18]22,23 (Table 1).…”