Cobalamin Deficiency in Children and Adolescents with Sickle Cell Disease.

Abstract

Background/Objective: Cobalamin (B₁₂) deficiency is reported in 18% of adults with sickle cell disease (SCD) and only 10% without SCD; limited data are available on children. Diagnosing B₁₂ deficiency is challenging given the lack of an established gold standard method of assessment and the unique renal features of SCD. B₁₂ metabolism can be impacted by the clinical use of nitrous oxide gas (N₂O), which is a standard therapy for SCD pain in some European countries. In response to emerging reports of neurologic sequalae in patients with SCD receiving N₂O, we evaluated the prevalence of B₁₂ deficiency in children with SCD pain. Methods: Secondary analysis of prospective blood and urine samples in children aged 3-21 hospitalized with SCD pain. B₁₂ deficiency was defined as plasma methylmalonic acid (MMA) > 592 nmol/L or urine MMA/creatinine ≥ 2.2 mmol/mol. Results: Ninety-four children (13 ± 4 years, 54% female, 68% hemoglobin-SS, and 72% on hydroxyurea) were assessed. Further, 53% (50/94) had B₁₂ deficiency diagnosed by either urine, plasma, or both; 27% (25/94) were deficient based on urine; 39% (37/94) were deficient by plasma; and 13% (12/94) were deficient by both plasma and urine. Plasma MMA and urine MMA/creatinine did not correlate with hemoglobin or mean corpuscular volume. Conclusions: B₁₂ deficiency was common in children with SCD. The absence of a gold standard for diagnosing B₁₂ deficiency compounded with the reliability issues of testing modalities make it impractical to determine whether this is an over- or under-estimation of the true prevalence. Future studies to better understand the dynamics of B₁₂ metabolism during acute and steady states in SCD are warranted and could elucidate the influence of acute SCD pain on these biomarkers.