Infantile hypercalcemia type 1 (HCINF1): a rare disease resulting in nephrolithiasis and nephrocalcinosis caused by mutations in the vitamin D catabolic enzyme, CYP24A1

J Endocrinol Invest. 2024 Nov;47(11):2663-2670. doi: 10.1007/s40618-024-02381-8. Epub 2024 May 23.

Abstract

Infantile hypercalcemia type 1 (HCINF1), formerly known as Lightwood syndrome, is a subtype of hypercalcemia caused by loss-of-function biallelic mutations in the vitamin D catabolic enzyme, CYP24A1, which 24-hydroxylates the hormone 1,25-(OH)2D3. This short review focuses on the main features of the HCINF1 disease; emerging knowledge of the structure and function of the cytochrome P450, CYP24A1 and the location of inactivating mutations; the development of a rapid LC-MS/MS-based laboratory test for defective 24-hydroxylation; and future implications for bioanalytical assay and treatment of all types of vitamin D-related hypercalcemic conditions.

Keywords: CYP24A1; HCINF-type 1; Hypercalcemia; Nephrocalcinosis; Nephrolithiasis; Vitamin D.

Publication types

  • Review

MeSH terms

  • Humans
  • Hypercalcemia* / diagnosis
  • Hypercalcemia* / genetics
  • Mutation*
  • Nephrocalcinosis* / diagnosis
  • Nephrocalcinosis* / etiology
  • Nephrocalcinosis* / genetics
  • Nephrolithiasis* / etiology
  • Nephrolithiasis* / genetics
  • Vitamin D / metabolism
  • Vitamin D3 24-Hydroxylase* / genetics

Substances

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

Supplementary concepts

  • Hypercalcemia, Infantile