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Background Measurement of vitamin B12 (B12) levels is routinely used to monitor B12 sufficiency. However, its accuracy may not be reliable in patients with short‐bowel syndrome (SBS). The presence of elevated methylmalonic acid (MMA) levels can also be used as a marker for B12 deficiency. Therefore, our aim was to analyze serum B12 and MMA levels simultaneously in a cohort of children with SBS to evaluate the accuracy of these markers in the assessment of B12 status. Methods Children ages 1–18 with intestinal failure were eligible for enrollment. MMA and B12 levels were checked simultaneously in all patients, with 93 sets of labs obtained over 2 years. Fifty percent of the patients were receiving parenteral nutrition. B12 injections were administered to 14 patients who had simultaneously elevated MMA and B12, and a repeat MMA level was measured 4–6 weeks after injection. Data were collected retrospectively. Results Forty‐eight percent of the lab pairs showed evidence of both elevated MMA and high or normal B12, which contradicted the expected inverse relationship of these markers. There was a statistically significant decrease in mean MMA values after treatment with B12 injections (412.7 vs 1037.5, P = 0.001). Conclusion Paradoxical elevation of MMA with normal or elevated serum B12 is common in children with SBS. Caution should be used when interpreting serum B12 and MMA values in this setting. This may be related to effects of small‐bowel bacterial overgrowth, a condition commonly seen in these patients.

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