Chapter 68 - Hereditary 1,25-dihydroxyvitamin D resistant rickets (VDDR-2A)

Abstract

Hereditary vitamin D resistant rickets (HVDRR) also known as vitamin D dependent rickets type 2A (VDDR-2A) is a rare metabolic bone disease caused by heterogeneous mutations in the gene for the vitamin D receptor (VDR). The clinical appearance is severe rickets in infancy, and some affected children also suffer from alopecia. The disease occurs most commonly in the setting of consanguinity, and the heterozygous parents are mostly asymptomatic. This chapter will discuss the clinical features of the disease, the cellular and mutational basis for the defects in the VDR, and the various forms of therapy that have been used to treat rickets. Two unique aspects of the disease, the alopecia in some cases, and the spontaneous improvement in the clinical picture around the time of puberty will be examined and recent research detailed. Finally, the possibility of the development or lack thereof of extra-skeletal diseases due to life long deprivation of vitamin D action will be discussed.