In this review, which evaluates the journey from the initial description of vitamin D-resistant rickets (XLH) to the regulation of renal phosphate transport, we (1) trace the timeline of important discoveries in unraveling the pathophysiology of XLH, (2) cite the recognized abnormalities in mineral metabolism in XLH, (3) evaluate factors that may affect parathyroid hormone values in XLH, (4) assess the potential interactions between the phosphate-regulating gene with homology to endopeptidase on the X chromosome and fibroblast growth factor 23 (FGF23) and their resultant effects on renal phosphate transport and vitamin D metabolism, (5) analyze the complex interplay between FGF23 and the factors that regulate FGF23, and (6) discuss the genetic and acquired disorders of hypophosphatemia and hyperphosphatemia in which FGF23 plays a role.
Parathyroid hormone (PTH) status in XLH has been controversial, with the prevailing belief that hyperparathyroidism develops in response to Pi therapy.
The findings in this study suggest that in patients with FHR, circulating PTH is required for the genetically transmitted abnormality to be physiologically expressed as a reduction in net renal reabsorption of phosphate, and that this physiological expression of the genetic abnormality is expressed fully at normal or nearly normal circulating levels of PTH.