New Perspectives on the Biology and Treatment of X-Linked Hypophosphatemic Rickets

Initial descriptions of hypophosphatemic rickets emphasized the poor clinical response to vitamin D, rather than the distinctive finding of marked hypophosphatemia.Such early descriptions became the basis for nomenclature of the rachitic disorders; so the name vitamin D-resistant rickets was widely used before the recognition that many cases were secondary to renal phosphate wasting.The name, vitamin D-resistant rickets, was well-entrenched by the time a more physiologic description was suggested.To add to the confusion, a target organ form of vitamin D resistance is now well characterized and is caused by mutations in the 1,25(OH),D3 receptor gene, analogous to other hormone-resistant states.This disorder of the 1,25(OH),D receptor, previously named vitamin D-dependent rickets, type 2 is increasingly referred to as hereditary resistance to vitamin D. Thus the currently preferred terminology for the hypophosphatemic disorder, X-linked kypopkospkatemic rickets (XLH) (or in some texts, familial hypophospkatemic rickets) distinguishes the condition from true biochemical resistance to vitamin D and refers to the primary mineral disturbance.A variety of hypophosphatemic rachitic disorders exist.The more frequently encountered disorders are secondary to inappropriate urinary excretion of phosphate.