PHEX

The PHEX gene encodes the phosphate-regulating neutral endopeptidase, which is involved in bone and dentin mineralization and renal phosphate reabsorption. Mutations in this gene are associated with X-linked hypophosphatemia (XLH), a disorder characterized by low levels of phosphate in the blood due to renal phosphate wasting.

Function

The PHEX protein is a member of the M13 family of zinc metalloendopeptidases. It is primarily expressed in bones and teeth, where it plays a crucial role in the regulation of phosphate homeostasis. The protein is involved in the degradation of fibroblast growth factor 23 (FGF23), a hormone that reduces renal phosphate reabsorption and decreases vitamin D synthesis.

Clinical Significance

Mutations in the PHEX gene lead to X-linked hypophosphatemia, the most common form of hereditary rickets. This condition is characterized by hypophosphatemia, rickets, and osteomalacia. Patients with XLH typically present with bone pain, deformities, and growth retardation. The disorder is inherited in an X-linked dominant manner.

Diagnosis

Diagnosis of XLH is based on clinical evaluation, biochemical tests showing low serum phosphate levels, and genetic testing to identify mutations in the PHEX gene. Radiographic imaging may reveal characteristic bone abnormalities.

Treatment

Management of XLH involves phosphate supplements and active vitamin D analogs to improve bone mineralization. Recently, burosumab, a monoclonal antibody against FGF23, has been approved for the treatment of XLH, offering a targeted therapeutic approach.

Research

Ongoing research is focused on understanding the precise mechanisms by which PHEX mutations lead to phosphate wasting and developing novel therapies to address the underlying pathophysiology of XLH.

See also

• Hypophosphatemic rickets
• Metabolic bone disease
• Endocrinology

External links

• PHEX gene - NCBI Gene
• PHEX - Genetics Home Reference