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When to suspect infantile hypercalcemia-1?

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Abstract

Purpose

The screening test to suspect infantile hypercalcemia-1 (HCINF1) is the measure of 25(OH)D3/24,25(OH)2D3 ratio at mass spectroscopy (MS). When the ratio is > 80, the gold standard for the diagnosis is genetic analysis. Given its limited availability, MS may not represent a screening test and most cases of HCINF1 remain undiagnosed. Aim of the study is to identify cut-offs of serum calcium and PTH useful to suspect patients with HCINF1.

Methods

We compared the levels of total serum calcium and PTH of 6 patients with HCINF1 harboring biallelic CYP24A1 pathogenic variants with 3 different control groups: (1) 12 subjects wild type for CYP24A1; (2) 12 subjects matched for age and sex; (3) 12 subjects matched for vitamin D levels. We validated the cut-offs, testing the number of adult patients affected by HCINF1 reported in the literature that could be identified using these cut-offs.

Results

A serum calcium level > 9.6 mg/dL showed the highest sensitivity (100%) and specificity (91%) in the comparison between homozygous and wild-type subjects. A serum PTH index < 0.315 showed the highest sensitivity (100%) and specificity (83.3%). A serum calcium level > 9.6 mg/dL was able to identify all adult HCINF1 patients whereas a PTH ratio < 0.315 identified 89.8% of the cases. Superimposable results were obtained using the other control groups.

Conclusion

Patients with serum calcium levels higher than 9.6 mg/dL and a PTH index lower than 0.315 are likely to be affected by HCINF1. Their diagnosis may be confirmed using MS and genetic analysis.

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Data availability

Some or all data generated or analyzed during this study are included in this published article or in the data repositories listed in References.

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Acknowledgements

The authors wish to thank the subjects involved in the study who graciously agreed to collaborate in the study.

Funding

This work was supported by Clinical Protocol Veristat PaTH Forward TCP-201

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Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, Unit of Endocrinology, University of Pisa, Pisa, Italy

    A. Brancatella, D. Cappellani, L. Pierotti, E. Dinoi, C. Sardella, S. Borsari, C. Marcocci & F. Cetani

  2. Department of Information Engineering, University of Pisa, Pisa, Italy

    P. Piaggi

  3. Endocrine Unit 2, Laboratory of Molecular Genetics, University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy

    F. Baldinotti & M A. Caligo

  4. Endocrine Unit, University Hospital of Pisa, Pisa, Italy

    F. Cetani

Authors
  1. A. Brancatella
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  2. D. Cappellani
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  3. L. Pierotti
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  4. E. Dinoi
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  5. C. Sardella
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  6. S. Borsari
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  7. P. Piaggi
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  8. F. Baldinotti
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  9. M A. Caligo
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  10. C. Marcocci
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  11. F. Cetani
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Contributions

AB and FC planned the study. PP and AB performed the statistical analysis. All authors discussed the results and revised the manuscript.

Corresponding author

Correspondence to F. Cetani.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration.

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Informed consent was obtained from all individual participants involved in the study.

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Brancatella, A., Cappellani, D., Pierotti, L. et al. When to suspect infantile hypercalcemia-1?. J Endocrinol Invest (2024). https://doi.org/10.1007/s40618-024-02312-7

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  • DOI: https://doi.org/10.1007/s40618-024-02312-7

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