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

J Pediatr Endocrinol Metab. 2023 Sep 29;36(11):999-1011. doi: 10.1515/jpem-2023-0147. Print 2023 Nov 27.


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; bisphosphonates; hypercalcemia; infant; vitamin D.

Publication types

  • Review

MeSH terms

  • Humans
  • Hypercalcemia* / diagnosis
  • Hypercalcemia* / drug therapy
  • Hypercalcemia* / etiology
  • Mutation
  • Vitamin D / metabolism
  • Vitamin D / therapeutic use
  • Vitamin D3 24-Hydroxylase / genetics
  • Vitamins


  • Vitamin D3 24-Hydroxylase
  • Vitamin D
  • Vitamins
  • CYP24A1 protein, human

Supplementary concepts

  • Hypercalcemia, Idiopathic, of Infancy
  • Hypercalcemia, Infantile