P0285 - Cobalamin deficiency in children with sickle cell disease: an unanticipated risk for use of nitrous oxide gas

Background: The prevalence of cobalamin (B12) deficiency in children with sickle cell disease (SCD) is unknown, however B12-deficiency has been reported in 18% of SCD-adults versus 10% in patients without SCD (Kamineni 2006). A higher frequency of B12-deficiency in SCD may be due to higher rates of hemolysis, erythrocyte turnover and folate deficiency. Nitrous oxide gas is commonly used for dental procedures and is standard therapy for sickle-related vaso-occlusive-pain in France. Recently we reported acute resolution of sickle-related priapism with nitrous therapy (Greenwald 2019). Although nitrous is generally considered safe, patients with B12-deficiency can experience serious neurologic complications, as nitrous impacts cobalamin metabolism. This study evaluates B12 status in children with SCD.

Methods: Urine samples were prospectively collected as part of a randomized-controlled trial of parenteral arginine therapy in children with SCD requiring admission for treatment of moderate-to-severe pain. Urine methylmalonic acid (MMA) level corrected for creatinine (Cr) reflecting B12 status, was measured via mass spectrometry. B12 deficiency was defined as MMA/Cr of 2.2-5, while severe B12 deficiency was reflected by MMA/Cr>5; MMA/Cr of 1.8-2.2 were considered possibly deficient while an MMA/Cr<1.8 was defined as normal B12 status.

Results: Ninety-four children with SCD and pain were enrolled. Median age was 13 years (Q1, Q3: 10, 16), 51% female, 68% Hb-SS, and 71% were on hydroxyurea (Table 1). Twenty-six percent (24/94) of patients demonstrated evidence of B12 deficiency, 25% of whom demonstrated a severe B12 deficiency (6/24). Another 7% (7/94) demonstrated possible deficiency. There were no statistically significant differences in age, gender, SCD genotype, hemoglobin levels, MCV or hydroxyurea use in those with and without B12 deficiency.

Conclusions: Approximately a quarter of children with SCD demonstrated evidence of B12-deficiency, which is higher than expected. Cobalamin deficiency is associated with a constellation of clinically relevant symptoms that may be overlooked in patients with SCD. In addition, these patients may be uniquely at risk for adverse neurological sequelae when receiving treatment with nitrous oxide gas. B12-deficiency is easily corrected with an intramuscular injection of methylcobalamin. Although further study in a larger cohort is needed, screening for B12 deficiency may be warranted in patients with SCD.