Hypophosphatemic nonrachitic bone disease: An entity distinct from X‐linked hypophosphatemia in the renal defect, bone involvement, and inheritance

Abstract

Abstract We have identified 5 patients with a condition which we call hypophosphatemic bone disease (HBD). The clinical findings, appearing during late infancy include modest shortening of stature, bowing of the lower limbs, and nonrachitic bone changes. The concentrations of calcium, parathyroid hormone (PTH), and vitamin D in serum and the basal excretion of cyclic AMP in urine are all normal. The serum phosphorus level is constantly depressed; inpaired reclamation of phosphate anion by kidneys explains this finding. Net tubular reabsorption of phosphate anion is “normal” at the low endogenous levels of filtered phosphate anion, yet below normal at elevated levels. The phosphaturic response to PTH infusion is abnormal in qualitative aspects. The characteristics of phosphate transport by kidney in HBD differ considerably from those described in X‐linked hypophosphatemia (XLH). The transport defect is not expressed in the (non‐epithelial) membrane of the erythrocyte. Since the severity of bone disease is quite different in HBD and XLH, and yet serum (extracellular) phosphorus concentration is similarly low in both diseases, we propose that some process regulates the distribution of phosphorus between serum and bone, and that this process is affected in different ways in HBD and XLH. In 2 pedigrees HBD is autosomal dominant with variable expression; the mode of inheritance is indeterminate in the other 3 families. The dominantly inherited hypophosphatemia is responsive to 1α OH analogues of vitamin D 3 . There is presumptive evidence from the pedigree studies, and in the response to vitamin D analogues, that HBD is not a single entity.