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Clinical heterogeneity and therapeutic options for idiopathic infantile hypercalcemia caused by CYP24A1 pathogenic variant

  • Zhichao Zheng ORCID logo , Yujie Wu , Huiping Wu , Jiahui Jin , Yue Luo , Shunshun Cao and Xiaoou Shan EMAIL logo
Published/Copyright: September 29, 2023
Journal of Pediatric Endocrinology and Metabolism
From the journal Journal of Pediatric Endocrinology and Metabolism Volume 36 Issue 11

Abstract

Objectives

Infantile hypercalcemia-1 (HCINF1) is a rare disease caused by pathogenic variants in the CYP24A1 gene, resulting in the inability to metabolize active vitamin D. This leads to hypercalcemia and severe complications.

Content

On December 8th, 2022, a systematic literature search was conducted in PubMed, Wanfang, and CNKI using the keywords “hypercalcemia” and “CYP24A1”. Data extraction included patient demographics, clinical presentation, treatment medications, and outcomes. The findings were synthesized to identify common patterns and variations among cases and to assess the efficacy of different therapies in reducing serum calcium. Our findings revealed two distinct peaks in the incidence of HCINF1 caused by CYP24A1 pathogenic variant. Kidney stones or renal calcifications were the most common clinical manifestations of the disease, followed by polyuria and developmental delay. Laboratory investigations showed hypercalcemia, elevated vitamin D levels, hypercalciuria, and low parathyroid hormone. Genetic analysis remains the only reliable diagnostic tool. Although there is no definitive cure for HCINF1, multiple drugs, including bisphosphonates, calcitonin, and rifampicin, have been used to control its symptoms. Blocking the production and intake of vitamin D is the preferred treatment option.

Summary and outlook

Our review highlights the basic clinical and biochemical features of HCINF1 and suggests that targeted diagnostic and therapeutic strategies are needed to address the clinical heterogeneity of the disease. The insights gained from this study may facilitate the development of innovative treatments for HCINF1.

Keywords: CYP24A1 ; hypercalcemia; vitamin D; bisphosphonates; infant
Corresponding author: Professor, Xiaoou Shan, Department of Pediatric Endocrinology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China, E-mail:

  1. Research ethics: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University.

  2. Informed consent: Informed consent was obtained from all individuals included in this study.

  3. Author contributions: All authors contributed to the study’s conception and design. Data collection, and analysis were performed by ZZ, XS, and YW. The first draft of the manuscript was written by ZZ and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

  4. Competing interests: Authors state no conflict of interest.

  5. Research funding: None declared.

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Received: 2023-05-08
Accepted: 2023-09-12
Published Online: 2023-09-29
Published in Print: 2023-11-27

© 2023 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. Clinical heterogeneity and therapeutic options for idiopathic infantile hypercalcemia caused by CYP24A1 pathogenic variant
  4. Original Articles
  5. Growth hormone use in pediatric inflammatory bowel disease
  6. Extremely and very preterm children who were born appropriate for gestational age show no differences in cortisol concentrations or diurnal rhythms compared to full-term children
  7. A prospective comparison study of subcutaneous and intramuscular testosterone injections in transgender male adolescents
  8. Excess body weight and dyslipidemia at well-child visit
  9. Body mass index evolution and ovarian function in adolescent girls who received GnRH agonist treatment for central precocious puberty or early and fast puberty
  10. Assessment of pubertal onset and disorders of puberty in Indian children and youth with type-1 diabetes
  11. A different approach to the evaluation of the genotype-phenotype relationship in biotinidase deficiency: repeated measurement of biotinidase enzyme activity
  12. Expected vs. perceived effects of gender-affirming hormone therapy among transmasculine adolescents
  13. Developmental scores in offspring of women with subclinical hypothyroidism in pregnancy are affected by gender and thyrotropin cutoff
  14. Assessment of the diagnosis, treatment, and follow-up of a group of Turkish pediatric glycogen storage disease type 1b patients with varying clinical presentations and a novel mutation
  15. IGAm: A novel index predicting long-term survival in patients with early-diagnosed inherited metabolic disorders
  16. Case Report
  17. Persistent hypercalcemia mimicking hypophosphatasia after discontinuation of a ketogenic diet: a case report
https://doi.org/10.1515/jpem-2023-0147
Keywords for this article
CYP24A1; hypercalcemia; vitamin D; bisphosphonates; infant

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. Clinical heterogeneity and therapeutic options for idiopathic infantile hypercalcemia caused by CYP24A1 pathogenic variant
  4. Original Articles
  5. Growth hormone use in pediatric inflammatory bowel disease
  6. Extremely and very preterm children who were born appropriate for gestational age show no differences in cortisol concentrations or diurnal rhythms compared to full-term children
  7. A prospective comparison study of subcutaneous and intramuscular testosterone injections in transgender male adolescents
  8. Excess body weight and dyslipidemia at well-child visit
  9. Body mass index evolution and ovarian function in adolescent girls who received GnRH agonist treatment for central precocious puberty or early and fast puberty
  10. Assessment of pubertal onset and disorders of puberty in Indian children and youth with type-1 diabetes
  11. A different approach to the evaluation of the genotype-phenotype relationship in biotinidase deficiency: repeated measurement of biotinidase enzyme activity
  12. Expected vs. perceived effects of gender-affirming hormone therapy among transmasculine adolescents
  13. Developmental scores in offspring of women with subclinical hypothyroidism in pregnancy are affected by gender and thyrotropin cutoff
  14. Assessment of the diagnosis, treatment, and follow-up of a group of Turkish pediatric glycogen storage disease type 1b patients with varying clinical presentations and a novel mutation
  15. IGAm: A novel index predicting long-term survival in patients with early-diagnosed inherited metabolic disorders
  16. Case Report
  17. Persistent hypercalcemia mimicking hypophosphatasia after discontinuation of a ketogenic diet: a case report
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