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Simultaneous measurement of 25(OH)-vitamin D and 24,25(OH)2-vitamin D to define cut-offs for CYP24A1 mutation and vitamin D deficiency in a population of 1200 young subjects

  • Etienne Cavalier EMAIL logo , Loreen Huyghebaert , Olivier Rousselle , Anne-Catherine Bekaert , Stéphanie Kovacs , Laura Vranken , Stéphanie Peeters , Caroline Le Goff and Aurélie Ladang
Published/Copyright: December 5, 2019

Abstract

Background

Simultaneous measurement of 25(OH)D and 24,25(OH)2D is a new tool for predicting vitamin D deficiency and allows evaluating CYP24A1 lack of function. Interpretation of 24,25(OH)2D should be performed according to 25(OH)D levels and a ratio, called the vitamin D metabolite ratio (VMR) has been proposed for such a purpose. Unfortunately, the VMR can be expressed in different ways and cannot be used if 24,25(OH)2D concentrations are undetectable. Here, we propose evaluating the enzyme activity taking into consideration the probability that a normal population presents undetectable 24,25(OH)2D concentrations according to 25(OH)D levels. We thus retrospectively measured 25(OH)D and 24,25(OH)2D in a population of 1200 young subjects to evaluate the 25(OH)D threshold above which the enzyme was induced.

Methods

Serum samples from 1200 infants, children, adolescent and young adults were used to simultaneously quantify 25(OH)D and 24,25(OH)2D by LCMS/MS.

Results

Median (interquartile range [IQR]) levels were 20.6 (14.4–27.2) ng/mL for 25(OH)D. 172 subjects (14.3%) presented 24,25(OH)2D values below the LOQ. When 25(OH)D values were <11 ng/mL, 63.1% of subjects presented undetectable 24,25(OH)2D concentrations. Percentage decreased with increasing 25(OH)D values to become 19.7% for 25(OH)D comprised between 12 and 15 ng/mL, 5.1% for 25(OH)D between 16 and 20 and 0.7% for 25(OH)D >21 ng/mL.

Conclusions

We suggest using a statistical approach to evaluate CYP24A1 function according to 25(OH)D concentrations. Our results also show that vitamin D deficiency, as defined biochemically, could be around 20 ng/mL in infants, children, adolescent and young adults and that vitamin D deficiency could be evaluated on a more individual basis.


Corresponding author: Pr. Etienne Cavalier, Department of Clinical Chemistry, University of Liège, CHU de Liège, Domaine du Sart-Tilman, 4000 Liège, Belgium, Phone: +32 4 3667692, Fax: +32 4 3667691
aCaroline Le Goff and Aurélie Ladang contributed equally to this work.
  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Schlingmann KP, Kaufmann M, Weber S, Irwin A, Goos C, John U, et al. Mutations in CYP24A1 and idiopathic infantile hypercalcemia. N Engl J Med 2011;365:410–21.10.1056/NEJMoa1103864Search in Google Scholar PubMed

2. Molin A, Baudoin R, Kaufmann M, Souberbielle JC, Ryckewaert A, Vantyghem MC, et al. CYP24A1 mutations in a cohort of hypercalcemic patients: evidence for a recessive trait. J Clin Endocrinol Metab 2015;100:E1343–52.10.1210/jc.2014-4387Search in Google Scholar PubMed

3. Kaufmann M, Gallagher JC, Peacock M, Schlingmann K-P, Konrad M, DeLuca HF, et al. Clinical utility of simultaneous quantitation of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D by LC-MS/MS involving derivatization with DMEQ-TAD. J Clin Endocrinol Metab 2014;99:2567–74.10.1210/jc.2013-4388Search in Google Scholar PubMed PubMed Central

4. Tai SS-C, Nelson MA. Candidate reference measurement procedure for the determination of (24R),25-dihydroxyvitamin D3 in human serum using isotope-dilution liquid chromatography-tandem mass spectrometry. Anal Chem 2015;87:7964–70.10.1021/acs.analchem.5b01861Search in Google Scholar PubMed

5. Wagner D, Hanwell HE, Schnabl K, Yazdanpanah M, Kimball S, Fu L, et al. The ratio of serum 24,25-dihydroxyvitamin D3 to 25-hydroxyvitamin D3 is predictive of 25-hydroxyvitamin D3 response to vitamin D3 supplementation. J Steroid Biochem Mol Biol 2011;126:72–7.10.1016/j.jsbmb.2011.05.003Search in Google Scholar PubMed

6. Berg AH, Powe CE, Evans MK, Wenger J, Ortiz G, Zonderman AB, et al. 24,25-Dihydroxyvitamin D3 and vitamin d status of community-dwelling Black and White Americans. Clin Chem 2015;61:877–84.10.1373/clinchem.2015.240051Search in Google Scholar PubMed PubMed Central

7. Herrmann M, Farrell C-J, Pusceddu I, Fabregat-Cabello N, Cavalier E. Assessment of vitamin D status – a changing landscape. Clin Chem Lab Med 2017;55:3–26.10.1515/cclm-2016-0264Search in Google Scholar PubMed

8. Aloia J, Fazzari M, Shieh A, Dhaliwal R, Mikhail M, Hoofnagle AN, et al. The vitamin D metabolite ratio (VMR) as a predictor of functional biomarkers of bone health. Clin Endocrinol (Oxf) 2017;86:674–9.10.1111/cen.13319Search in Google Scholar PubMed PubMed Central

9. Seidowsky A, Villain C, Vilaine E, Baudoin R, Tabarin A, Kottler M-L, et al. Hypercalcémie par mutation inactivatrice du CYP24A1. Étude d’un cas et revue de la littérature. Néphrol Thér 2017;13:146–53.10.1016/j.nephro.2017.01.019Search in Google Scholar PubMed

10. Ginsberg C, Katz R, de Boer IH, Kestenbaum BR, Chonchol M, Shlipak MG, et al. The 24,25 to 25-hydroxyvitamin D ratio and fracture risk in older adults: the cardiovascular health study. Bone 2017;107:124–30.10.1016/j.bone.2017.11.011Search in Google Scholar PubMed PubMed Central

11. Ketha H, Thacher TD, Oberhelman SS, Fischer PR, Singh RJ, Kumar R. Comparison of the effect of daily versus bolus dose maternal vitamin D3 supplementation on the 24,25-dihydroxyvitamin D 3 to 25-hydroxyvitamin D 3 ratio. Bone 2018;110:321–5.10.1016/j.bone.2018.02.024Search in Google Scholar PubMed PubMed Central

12. Selamet U, Katz R, Ginsberg C, Rifkin DE, Fried LF, Kritchevsky SB, et al. Serum calcitriol concentrations and kidney function decline, heart failure, and mortality in elderly community-living adults: the health, aging, and body composition study. Am J Kidney Dis 2018;72:419–28.10.1053/j.ajkd.2018.03.026Search in Google Scholar PubMed PubMed Central

13. Fabregat-Cabello N, Farre-Segura J, Huyghebaert L, Peeters S, Le Goff C, Souberbielle J-C, et al. A fast and simple method for simultaneous measurements of 25(OH)D, 24,25(OH) 2 D and the vitamin D metabolite ratio (VMR) in serum samples by LC-MS/MS. Clin Chim Acta 2017;473:116–23.10.1016/j.cca.2017.08.024Search in Google Scholar PubMed

Received: 2019-09-24
Accepted: 2019-11-06
Published Online: 2019-12-05
Published in Print: 2020-01-28

©2019 Walter de Gruyter GmbH, Berlin/Boston

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