Clinical and biochemical findings in parents of children with vitamin D‐dependent rickets type II

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.