PHEX

Hereditary hypophosphatemic rickets

More than 200 mutations in the PHEX gene have been found to cause the most common form of hereditary hypophosphatemic rickets, which is known as X-linked hypophosphatemic rickets. These mutations inactivate the PHEX enzyme, leaving it unable to cleave other proteins.

Researchers are uncertain how mutations in the PHEX gene lead to low levels of phosphate in the blood (hypophosphatemia) and related problems with bone growth in people with X-linked hypophosphatemic rickets. Because many affected individuals have increased levels of fibroblast growth factor 23, it is likely that PHEX gene mutations somehow alter the production of that protein. An increase in fibroblast growth factor 23 reduces phosphate reabsorption by the kidneys, leading to hypophosphatemia. However, because some affected individuals have normal levels of fibroblast growth factor 23, researchers are also considering other pathways by which a mutated PHEX gene could result in X-linked hypophosphatemic rickets.