Presymptomatic diagnosis of CYP24A1-related infantile idiopathic hypercalcemia: A case report

Eur J Med Genet. 2020 Dec;63(12):104100. doi: 10.1016/j.ejmg.2020.104100. Epub 2020 Nov 10.


Vitamin D plays an important role in calcium homeostasis and bone mineralization. Inefficient inactivation of vitamin D leads to a condition called idiopathic infantile hypercalcemia (IIH). In the last decade mutations in CYP24A1, the gene responsible for vitamin D inactivation, were described as the main molecular cause of IIH. In this study, we present a family with two daughters diagnosed with IIH due to two different mutations in CYP24A1 gene. Based on next-generation sequencing (NGS), the elder daughter was diagnosed as carrying the mutations CYP24A1: c.1186C > T; (p.Arg396Trp) and c.428_430del; (p.Glu143del). Within this context, we were able to presymptomatically diagnose her newborn sister using Sanger sequencing technique. Screening for CYP24A1 mutations in families with IIH history helps preventing disease manifestations in newborn siblings. Thus, NGS combined with Sanger sequencing validation opens up the perspective of preventive medicine with great impact on IIH management, where stopping vitamin D administration is enough to prevent disease manifestation, in most cases.

Keywords: CYP24A1; Infantile idiopathic hypercalcemia; NGS; Sanger sequencing.

Publication types

  • Case Reports

MeSH terms

  • Asymptomatic Diseases
  • Child
  • Female
  • Gene Deletion
  • Genetic Carrier Screening / methods*
  • Humans
  • Hypercalcemia / diagnosis
  • Hypercalcemia / genetics*
  • Mutation, Missense
  • Pedigree
  • Vitamin D / metabolism
  • Vitamin D3 24-Hydroxylase / genetics*


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

Supplementary concepts

  • Hypercalcemia, Infantile