title: Clinical and biochemical findings in parents of children with vitamin D-dependent rickets Type II.
abstract: Vitamin D-dependent rickets type II is a rare disease caused by a disorder of the receptor for 1, 25-dihydroxyvitamin D (1, 25(OH)2D). Several parameters of this receptor-effector system were investigated to obtain biochemical information on the presumed heterozygotes of vitamin D-dependent rickets type II in parents of five patients and in their age-matched controls. It was found that the serum concentrations of 1, 25-(OH)2D and 24,25-dihydroxy-vitamin D (24,25(OH)2D), and the ratio of 1,25-(OH)2D/24,25-(OH)2D differed significantly in the parents from those of the patients and the respective control groups. In the parents' cultured skin fibroblasts, the activity of 25-hydroxyvitamin D-24-hydroxylase induced by 10(-8) mol/L 1, 25-(OH)2D3 ranged from 50 to 82% of that of their controls (versus 1-13% of controls for the patients). The binding capacity of the parents' [3H]1, 25-(OH)2D3 to the nucleus was 38-54% of that of their control subjects (versus 7-27% of controls for the patients). The parents' values were thus in a range between those of the patients and the control groups. These findings suggest that, in the parents, a partial impairment of the receptor system for 1, 25-(OH)2D led to an imbalance of vitamin D metabolism, thus confirming that vitamin D-dependent rickets type II is an autosomal recessive inherited disease. Serum concentrations of 1, 25-(OH)2D and 24, 25-(OH)2D may provide useful parameters for detecting heterozygotes of this disease.
authors.affiliation: Department of Paediatrics, School of Medicine, University of Tokushima, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Yokota
authors.forename: E
authors.initials: E
authors.lastname: Takeda
authors.forename: M
authors.initials: M
authors.lastname: Ito
authors.forename: H
authors.initials: H
authors.lastname: Kobashi
authors.forename: T
authors.initials: T
authors.lastname: Saijo
authors.forename: Y
authors.initials: Y
authors.lastname: Kuroda
mesh_terms: D015650:24,25-Dihydroxyvitamin D 3 / Q000097:blood; D002117:Calcitriol / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005347:Fibroblasts / Q000201:enzymology / Q000648:ultrastructure; D006580:Genetic Carrier Screening; D006801:Humans; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000235:genetics* / Q000378:metabolism; D012279:Rickets / Q000235:genetics*; D013250:Steroid Hydroxylases / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D015650:24,25-Dihydroxyvitamin D 3; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol