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C-3 Epimers Can Account for a Significant Proportion of Total Circulating 25-Hydroxyvitamin D in Infants, Complicating Accurate Measurement and Interpretation of Vitamin D Status

Departments of Laboratory Medicine and Pathology (R.J.S., R.L.T., S.K.G.G.) and Medicine (S.K.G.G.), Mayo Clinic, Rochester, Minnesota 55905; and Epimer, LLC (G.S.R.), Providence, Rhode Island 02906

Address all correspondence and requests for reprints to: Stefan K. G. Grebe, Mayo Clinic, 200 1st Street SW, Rochester, Minnesota 55905. E-mail: grebe.stefan{at}mayo.edu.

Context: We have recently introduced liquid chromatography-tandem mass spectrometry (LC-MS/MS) for 25-hydroxyvitamin D₂ (25OHD₂) and 25OHD₃ testing. During subsequent clinical use, we identified significantly elevated results in some infants. We hypothesized this might represent assay interference caused by C-3 epimers of 25OHD₂ or 25OHD₃.

Objective: Our aims were to 1) determine the prevalence of C-3 epimers of 25OHD₂ or 25OHD₃ in human serum, and 2) identify the patient populations that might be affected.

Study Design: We modified our LC-MS/MS method to allow detection of C-3 epimers. We retested specimens from four patient groups with the new method and an extracted RIA: 1) children less than 1 yr old, 2) children 1–18 yr old, 3) adults aged 20–87 yr with liver disease, and 4) adults aged 19–91 yr without liver disease.

Results: In 172 children from group 1 with detectable 25OHD₂ or 25OHD₃, we identified C-3 epimers in 39 (22.7%). The epimers contributed 8.7–61.1% of the total 25-OHD. There was an inverse relationship between patient age and epimer percentage (r = 0.48; P < 0.002). The RIA gave accurate 25-OHD results that correlated with the modified LC-MS/MS method. No C-3 epimers were detected in any of the other groups.

Conclusions: Significant concentrations of C-3 epimers of 25OHD₂ or 25OHD₃ are commonly found in infants. This can lead to overestimation of 25-OHD levels. Measurements in children less than 1 yr should therefore be performed with an assay that allows accurate detection of 25-OHD in the presence of its C-3 epimers.

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