Genetic disorders of Vitamin D biosynthesis and degradation.

Abstract	Vitamin D, an inactive secosteroid pro-hormone, is produced by the action of ultraviolet light on 7-dehydrocholesterol in the skin. The active hormone, 1,25(OH)2D is produced by sequential 25-hydroxylation in the liver, principally by CYP2R1, and 1α-hydroxylation in the kidney by CYP27B1. Mutations in CYP27B1 cause 1α-hydroxylase deficiency, also known as vitamin D dependent rickets type I or hereditary pseudo-vitamin D deficient rickets; very rare mutations in CYP2R1 can cause 25-hydroxylase deficiency. Both deficiencies cause hypocalcemia, secondary hyperparathyroidism, severe rickets in infancy, and low serum concentrations of 1,25(OH)2D; both disorders respond to hormonal replacement therapy with calcitriol. The inactivation of vitamin D is principally initiated by its 23- and 24-hydroxylation by CYP24A1. Mutations in CYP24A1 can cause both severe neonatal hypercalcemia and a less severe adult hypercalcemic syndrome. Other pathways of vitamin D metabolism are under investigation, notably its 20-hydroxylation by the cholesterol side-chain cleavage enzyme, CYP11A1.
Authors	Walter L Miller
Journal	The Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 165 Issue Pt A Pg. 101-108 (01 2017) ISSN: 1879-1220 [Electronic] England
PMID	27060335 (Publication Type: Journal Article, Review)
Copyright	Copyright Â© 2016 Elsevier Ltd. All rights reserved.
Chemical References	Dehydrocholesterols Steroids Vitamin D Cholesterol 7-dehydrocholesterol Cytochrome P450 Family 2 CYP2R1 protein, human Cholestanetriol 26-Monooxygenase CYP24A1 protein, human Vitamin D3 24-Hydroxylase 25-Hydroxyvitamin D3 1-alpha-Hydroxylase CYP27B1 protein, human Cholesterol Side-Chain Cleavage Enzyme Calcitriol
Topics	25-Hydroxyvitamin D3 1-alpha-Hydroxylase (genetics) Animals Calcitriol (chemistry) Cell Proliferation Cholestanetriol 26-Monooxygenase (genetics) Cholesterol (metabolism) Cholesterol Side-Chain Cleavage Enzyme (genetics) Cytochrome P450 Family 2 (genetics) DNA Mutational Analysis Dehydrocholesterols (metabolism) Humans Hypercalcemia (genetics) Mice Mutation Rats Rickets (diagnosis, genetics) Steroids (metabolism) Ultraviolet Rays Vitamin D (biosynthesis, metabolism) Vitamin D3 24-Hydroxylase (genetics)

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