Hereditary 1,25-Dihydroxyvitamin D-resistant rickets.

Abstract

Abstract Multiple different mutations in various domains along the vitamin D receptor (VDR) gene are the basis of hereditary 1,25-dihydroxyvitamin -resistant rickets (HVDRR), also known as vitamin D-dependent rickets type II. HVDRR is characterized by early onset hypocalcemia, secondary hyperparathyroidism and elevated serum 1,25(OH)2D concentrations and unresponsiveness (resistance) to endogenous or exogenous 1,25(OH)2D in infants. Parents, often heterozygote carriers, are essentially normal and the recessive disease is often found in the setting of consanguinity. The disease may also be characterized by the presence of alopecia in some children depending on the location of the mutation. Treatment of HVDRR often requires high doses of calcium administered either intravenously or orally to bypass the defect in VDR signaling. Calcium therapy can successfully reverse the metabolic abnormalities and heal the rachitic changes in the bones. However, it is now clear that many children “outgrow” the metabolic abnormalities in their teens or as adults and eventually no longer require therapy. The alopecia, if present, remains permanently despite normalization of calcium and bone.