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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\u201321 hospitalized with SCD pain. B12 deficiency was defined as plasma methylmalonic acid (MMA) &gt; 592 nmol\/L or urine MMA\/creatinine \u2265 2.2 mmol\/mol. Results: Ninety-four children (13 \u00b1 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.<\/jats:p>","DOI":"10.3390\/nu17030597","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T09:54:38Z","timestamp":1738835678000},"page":"597","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cobalamin Deficiency in Children and Adolescents with Sickle Cell Disease"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6685-2902","authenticated-orcid":false,"given":"Dunia","family":"Hatabah","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Krieger","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9745-0619","authenticated-orcid":false,"given":"Lou Ann","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8697-7186","authenticated-orcid":false,"given":"Frank","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rawan","family":"Korman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8863-714X","authenticated-orcid":false,"given":"Loretta","family":"Reyes","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Children\u2019s Healthcare of Atlanta, Atlanta, GA 30329, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine","family":"Umana","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Benedit","sequence":"additional","affiliation":[{"name":"Children\u2019s Healthcare of Atlanta, Atlanta, GA 30329, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget A.","family":"Wynn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris A.","family":"Rees","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Children\u2019s Healthcare of Atlanta, Atlanta, GA 30329, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7738-2620","authenticated-orcid":false,"given":"Carlton","family":"Dampier","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Children\u2019s Healthcare of Atlanta, Atlanta, GA 30329, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6019-2858","authenticated-orcid":false,"given":"Claudia R.","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Children\u2019s Healthcare of Atlanta, Atlanta, GA 30329, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,6]]},"reference":[{"key":"ref_1","first-page":"352","article-title":"Low cobalamin levels in African Americans with and without sickle cell disease","volume":"98","author":"Kamineni","year":"2006","journal-title":"J. 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