Genetic disorders and defects in vitamin d action

Endocrinol Metab Clin North Am. 2010 Jun;39(2):333-46, table of contents. doi: 10.1016/j.ecl.2010.02.004.


Two rare genetic diseases can cause rickets in children. The critical enzyme to synthesize calcitriol from 25-hydroxyvitamin D, the circulating hormone precursor, is 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-hydroxylase). When this enzyme is defective and calcitriol can no longer be synthesized, the disease 1alpha-hydroxylase deficiency develops. The disease is also known as vitamin D-dependent rickets type 1 or pseudovitamin D deficiency rickets. When the VDR is defective, the disease hereditary vitamin D-resistant rickets, also known as vitamin D-dependent rickets type 2, develops. Both diseases are rare autosomal recessive disorders characterized by hypocalcemia, secondary hyperparathyroidism, and early onset severe rickets. In this article, these 2 genetic childhood diseases, which present similarly with hypocalcemia and rickets in infancy, are discussed and compared.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / deficiency*
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics*
  • Alopecia / genetics
  • Animals
  • Calcitriol / biosynthesis*
  • Calcitriol / genetics*
  • Calcitriol / therapeutic use
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Hyperparathyroidism, Secondary / genetics
  • Hypocalcemia / genetics
  • Infant
  • Infant, Newborn
  • Male
  • Mice
  • Receptors, Calcitriol / genetics*
  • Rickets / genetics*
  • Rickets / metabolism
  • Rickets / pathology


  • Receptors, Calcitriol
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • Calcitriol