Genetic Diseases of Vitamin D Metabolizing Enzymes

Endocrinol Metab Clin North Am. 2017 Dec;46(4):1095-1117. doi: 10.1016/j.ecl.2017.07.011. Epub 2017 Oct 5.

Abstract

Vitamin D metabolism involves 3 highly specific cytochrome P450 (CYP) enzymes (25-hydroxylase, 1α-hydroxylase, and 24-hydroxylase) involved in the activation of vitamin D3 to the hormonal form, 1,25-(OH)2D3, and the inactivation of 1,25-(OH)2D3 to biliary excretory products. Mutations of the activating enzymes CYP2R1 and CYP27B1 cause lack of normal 1,25-(OH)2D3 synthesis and result in rickets whereas mutations of the inactivating enzyme CYP24A1 cause build-up of excess 1,25-(OH)2D3 and result in hypercalcemia, nephrolithiasis, and nephrocalcinosis. This article reviews the literature for 3 clinical conditions. Symptoms, diagnosis, treatment, and management of vitamin D-dependent rickets and idiopathic infantile hypercalcemia are discussed.

Keywords: Cytochrome P450; Hypercalcemia; Rickets; Vitamin D metabolism.

Publication types

  • Review

MeSH terms

  • Cholestanetriol 26-Monooxygenase / genetics*
  • Cholestanetriol 26-Monooxygenase / metabolism
  • Cytochrome P450 Family 2 / genetics*
  • Cytochrome P450 Family 2 / metabolism
  • Humans
  • Hypercalcemia / diagnosis
  • Hypercalcemia / genetics*
  • Hypercalcemia / metabolism
  • Infant, Newborn, Diseases / diagnosis
  • Infant, Newborn, Diseases / genetics*
  • Infant, Newborn, Diseases / metabolism
  • Metabolism, Inborn Errors / diagnosis
  • Metabolism, Inborn Errors / genetics*
  • Metabolism, Inborn Errors / metabolism
  • Mutation*
  • Rickets / diagnosis
  • Rickets / genetics*
  • Rickets / metabolism
  • Vitamin D3 24-Hydroxylase / genetics*
  • Vitamin D3 24-Hydroxylase / metabolism

Substances

  • Cytochrome P450 Family 2
  • CYP2R1 protein, human
  • Cholestanetriol 26-Monooxygenase
  • Vitamin D3 24-Hydroxylase

Supplementary concepts

  • Hypercalcemia, Idiopathic, of Infancy