<unk>  <unk> , is an<unk> -linked dominant form of rickets (or osteomalacia) that differs from most cases of rickets in that vitamin D supplementation does not cure it. It can cause bone deformity including short stature and genu varum (bow-leggedness). It is associated with a mutation in the PHEX gene sequence <unk> p.22) and subsequent inactivity of the PHEX protein. PHEX mutations lead to an elevated circulating (systemic) level of the hormone FGF23 which results in renal phosphate wasting, and locally in the extracellular matrix of bones and teeth an elevated level of the mineralization/calcification-inhibiting protein osteopontin. Mutations in the PHEX gene result in an increase in systemic circulating FGF23 and a decrease in the enzymatic activity of the PHEX protein such that mineralization-inhibiting osteopontin accumulates locally in bones and teeth causing osteomalacia and odontomalacia. For<unk>  and hypophosphatasia, such inhibitor-enzyme pair relationships function to regulate mineralization in the extracellular matrix through a double-negative (inhibiting inhibitors) activation effect in a manner described as the Stenciling Principle. Both these underlying mechanisms (renal phosphate wasting systemically, and mineralization inhibitor accumulation locally) contribute to the pathophysiology of<unk>  that leads to soft bones and teeth (hypomineralization, osteomalacia/odontomalacia). The prevalence of the disease is 1 in 20,000.<unk>  may be lumped in with Autosomal dominant<unk>  rickets under general terms such as<unk>  rickets.<unk>  rickets are associated with at least nine other genetic mutations. Clinical management of<unk>  rickets may differ depending on the specific mutations associated with an individual case, but treatments are aimed at raising phosphate levels to promote normal bone formation.
X-linked hypophosphatemia
Autosomal dominant hypophosphatemic rickets
Pseudohypoparathyroidism
X-linked recessive hypoparathyroidism
Eruptive hypomelanosis
Hypoparathyroidism
Malignant infantile osteopetrosis
Pseudopseudohypoparathyroidism