Hypercobalaminemia in children: clinical characteristics and ınherited metabolic diagnoses in a tertiary-center...

Elevated serum vitamin B12 concentrations are commonly attributed to vitamin supplementation and are often considered a benign laboratory finding. However, persistent hypercobalaminemia may reflect underlying disease processes, including inherited metabolic disorders (IMDs). Data regarding the clinical significance of elevated vitamin B12 levels in patients with IMDs remain limited. To describe the clinical and diagnostic characteristics of children with elevated serum vitamin B12 concentrations evaluated at a tertiary pediatric metabolic center, with particular attention to confirmed inherited metabolic disorders and documented prescribed vitamin B12 treatment. This retrospective study included 185 patients with serum vitamin B12 concentrations ≥ 910 pg/mL who were evaluated at a tertiary pediatric metabolic referral center between September 2022 and January 2026. Diagnoses were categorized as confirmed inherited metabolic disorder (IMD), probable/provisional IMD, non-metabolic genetic disorder, or unresolved. Patients were then grouped according to confirmed IMD status and documented prescribed vitamin B12 treatment. Demographic characteristics, laboratory findings, organ involvement, and available longitudinal vitamin B12 measurements were analyzed. Among 185 patients with elevated serum vitamin B12 concentrations, 52 (28.1%) met the criteria for a confirmed IMD. The four analysis groups comprised confirmed IMD without documented prescribed vitamin B12 treatment (n = 23), no confirmed IMD without documented prescribed vitamin B12 treatment (n = 106), confirmed IMD with documented prescribed vitamin B12 treatment (n = 29), and no confirmed IMD with documented prescribed vitamin B12 treatment (n = 27). In Group 1, the median initial concentration was 2000 pg/mL (IQR 1881-2000). Prespecified pairwise comparisons showed higher initial vitamin B12 concentrations in Group 1 than in Group 2 (Holm-adjusted p = 0.032), whereas comparisons with Groups 3 and 4 were not significant. The confirmed IMD spectrum included organic acidemias, amino acid metabolism disorders, mitochondrial disorders, lysosomal and peroxisomal disorders, glycogen storage disease, Wilson disease, and other defined metabolic conditions. Longitudinal observations were heterogeneous and were available for only a subset of patients; they are therefore presented as illustrative cases rather than evidence of a general pattern.

This study provides a descriptive characterization of a selected tertiary-center cohort with elevated serum vitamin B12 concentrations. Confirmed IMDs were present in 28.1% of the cohort, including 23 children without documented prescribed vitamin B12 treatment. In the absence of a contemporaneous normal-vitamin-B12 control group or an unselected IMD cohort, these findings do not establish prevalence, discrimination, diagnostic accuracy, or an epidemiological association.

• Elevated serum vitamin B12 concentrations in children are commonly attributed to supplementation, althoughpersistent unexplained hypercobalaminemia may be associated with underlying disease.. • Evidence regarding the clinical signifi cance of hypercobalaminemia and its relationship with inherited metabolicdisorders in children remains limited..

• In this selected tertiary pediatric metabolic center cohort, 52 of 185 children (28.1%) met the prespecifi ed criteriafor a confi rmed inherited metabolic disorder; among patients without documented prescribed vitamin B12 treatment,organic acidemias and mitochondrial disorders were the most frequently represented diagnostic categories. • Persistent unexplained hypercobalaminemia is a nonspecifi c biochemical fi nding that may prompt consideration ofan inherited metabolic disorder only in children with compatible clinical features.