Prevalence and Clinical Correlations of Cyanocobalamin Deficiency in Adults with Sickle Cell Disease: A Single Center Cross-Sectional Study

Introduction

Vitamin B12 (cyanocobalamin) is crucial for red blood cell formation, neurological function, and DNA synthesis. Patients with sickle cell disease (SCD) experience rapid red blood cell turnover and increased erythropoiesis, which can deplete B12 reserves and exacerbate hematological complications. Although folic acid supplementation is commonly used to support red blood cell production in SCD, it can mask B12 deficiencies, leading to delayed diagnosis and treatment. Untreated B12 deficiency can result in severe neurological and hematological issues. Despite this, routine screening for B12 levels is not widely implemented for SCD patients. This study aims to determine the prevalence of B12 deficiency in adults with SCD at a comprehensive sickle cell center and to explore the relationship between B12 levels and neurological symptoms, along with other clinical and laboratory correlations.

Methods

This cross-sectional study was conducted from May to July 2024 at our institution, including SCD patients aged 18 and older who had undergone B12 screening within the past year. We collected demographic data and medical histories, focusing on hemoglobin genotype and neurologic symptoms. B12 levels were classified as normal (≥400 pg/mL), borderline (300-399 pg/mL), or deficient (<300 pg/mL). We used descriptive statistics to summarize the data and applied Chi-square or Fisher's exact tests and t-tests for comparisons, considering a P-value <0.05 as significant. Analysis was performed using STATA version 18.

Results

The study included 100 adult SCD patients. The gender distribution was approximately 60% female in both the borderline/deficient and normal B12 groups, with a racial composition predominantly Black (98%). Hemoglobin genotype distribution differed significantly between the groups (P = 0.039), indicating a possible interaction between SCD severity and B12 deficiency. Patients with B12 deficiencies were more likely to be prescribed supplements (85.2% vs. 9.6%; P < 0.001). Neurologic symptoms were more common in the normal group (35.6% vs. 22.2%), although not significantly (P = 0.20). Laboratory results showed no significant differences except in hemoglobin S percentage (P = 0.028). Vitamin D deficiency was prevalent in 80% of those with B12 deficiencies and 90.4% with normal levels.

Conclusion

This study highlights a significant prevalence of B12 deficiency (27%) among adults with SCD at our center, underlining the need for routine B12 screening. Despite a high prevalence of vitamin D deficiency across all patients, there was no significant correlation between vitamin D and B12 levels, suggesting independent pathways of deficiency. The consistent use of folic acid, which may mask B12 deficiency symptoms, and the higher incidence of neurologic symptoms in patients with normal B12 levels warrant further investigation to better understand the relationship between B12 levels and neurological outcomes in SCD.

Idowu:GBT: Consultancy, Other: Advisory board or panel, Research Funding, Speakers Bureau; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Other: Advisory board or panel, Research Funding; Agios Pharmaceuticals, Inc.: Research Funding; Forma: Research Funding; Novartis: Consultancy, Research Funding; Alexion: Research Funding; bluebird bio Pharmaceuticals: Consultancy; Vertex: Consultancy.