[Familial hypophosphatemic rickets]

Familiar hypophosphatemic rickets (FHR) is characterized by isolated defect of renal phosphate reabsorption, hypophosphataemia, rickets and poor growth. In untreated cases parathyroid hormone and calcitriol levels are normal. FHR is caused by mutations of the PHEX gene encoding a zinc-binding metalloprotease enzyme. PHEX is expressed in bones and the parathyroid gland but not in the kidney. The gene product is involved in the inactivation of a phosphate regulating hormone (phosphatonin). The presence of this hormone through unknown mechanisms decreases the sodium-dependent phosphate cotransporter in the kidney resulting in impaired phosphate transport. In addition the PHEX gene product exerts autocrine and paracrine effects on the bone. Despite recent advances in the understanding of the pathomechanism, treatment of FHR is still symptomatic. It consists of active vitamin D analogues and oral phosphate supplementation. Nephrocalcinosis is a well-known, usually non-progressive side effect of the conventional therapy. As shown by pilot studies, poorly growing children with FHR may benefit from the positive effect of human recombinant growth hormone (rhGH). However, rhGH treatment could aggravate the already existing tendency to disproportionate growth resulting in the overgrowth of the trunk. The disturbed phosphate homeostasis persists during the whole life span of the FHR patients. It is therefore essential to provide lifelong care, to prevent late skeletal and dental consequences or to treat them if already established. That care should be done by the teamwork of the pediatrician, internist, orthopedist, dentist and the psychologist.