Diagnosis and Management of Vitamin D Dependent Rickets

Abstract

The term "vitamin D dependent rickets" describes a group of genetic disorders that are characterized by early-onset rickets due to the inability to maintain adequate concentrations of active forms of vitamin D or a failure to respond fully to activated vitamin D. Although the term is now admittedly a pathophysiological misnomer, there remains clinical relevance for its continued use, as patients have a lifelong "dependency" on administration of specialized regimens of vitamin D replacement. This review provides an update on the molecular bases for the three forms of vitamin D dependent rickets, and summarizes current protocols for management of affected subjects.

Keywords: Vitamin D; genetics; hypocalcemia; rickets; treatment.

Figure 1

Vitamin D homeostasis and genetic blocks in VDDR. The figure shows the overall metabolic control of vitamin D homeostasis, with the genes involved in various forms of VDDR shown in bold.

Figure 2

A diagnostic algorithm for evaluation of a child with radiological or clinical features of rickets. See text for complete description of biochemical and clinical features of each form of rickets. PLP, Pyridoxal 5′-phosphate, the metabolically active form of vitamin B6; sPi, serum phosphorus; TFTs, thyroid function tests; PLP, pyridoxal 5′ phosphate (vitamin B6); ALPL, the gene for tissue non-specific alkaline phosphatase.