Genetic disorders and defects in vitamin d action.
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.
Division of Endocrinology, Gerontology and Metabolism, Stanford University School of Medicine, Stanford University, S-025 Endocrinology, Stanford, CA 94305-5103, USA. pjmalloy@stanford.edu
Peter J
PJ
Malloy
David
D
Feldman
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000172:deficiency* / Q000235:genetics*; D000505:Alopecia / Q000235:genetics; D000818:Animals; D002117:Calcitriol / Q000096:biosynthesis* / Q000235:genetics* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000235:genetics; D006996:Hypocalcemia / Q000235:genetics; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D018167:Receptors, Calcitriol / Q000235:genetics*; D012279:Rickets / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D018167:Receptors, Calcitriol; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol