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X-linked hypophosphatemia
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

X-linked hypophosphatemia

X-linked hypophosphatemia is a condition characterized by low blood phosphate levels, which can lead to weakened bones, rickets in children, and osteomalacia in adults.

Overview

X-linked hypophosphatemia is characterized by low levels of phosphate in the blood (hypophosphatemia). Phosphate is a mineral essential for the development of bones and teeth. Without adequate phosphate, bones can weaken or soften, leading to rickets in growing children or osteomalacia in adults.

Symptoms

Features vary widely, even within the same family. Symptoms may include:

  • Skeletal abnormalities: Slow growth in early childhood, short stature, and abnormally curved (bowed) legs.
  • Adult complications: Osteomalacia, which increases the risk of painful stress fractures.
  • Joint issues: Abnormal calcium deposits near joints (enthesopathy) and osteoarthritis.
  • Dental and cranial issues: Dental abscesses and premature fusion of skull bones (craniosynostosis).
  • Rare complications: Spinal abnormalities, including narrowing of the spinal canal or the formation of fluid-filled cysts (syrinx) within the spinal cord.

Causes

The condition is caused by variants in the PHEX gene. This gene provides instructions for an enzyme important for bone and tooth development. Variants in PHEX lead to an increase in fibroblast growth factor 23. This protein impairs the body's ability to absorb phosphate in the intestines and reabsorb it in the kidneys, resulting in lower levels of phosphate available for bone maintenance.

Inheritance

This condition is inherited in an X-linked pattern. Because the PHEX gene is located on the X chromosome, a single variant in males is typically sufficient to cause the condition. Females with one PHEX variant typically experience symptoms similar to those seen in males. Fathers pass the variant to all of their daughters and none of their sons, while mothers have a 50 percent chance of passing the variant to each child.

Frequently Asked Questions

Children with XLH have poor dentin mineralization, making them vulnerable to spontaneous pulp infections. Ensure a dental exam every 6 months, use fluoride toothpaste (1,350 ppm for children over 2 years), and consider a dental sealant on molars. Prompt treatment of any caries, and in some cases prophylactic root canal therapy of primary teeth, can prevent abscess formation.
Watch for new back pain, numbness, weakness in the legs, or changes in gait, which may signal spinal stenosis or a syrinx. Routine surveillance includes a standing spine X‑ray every 1–2 years to assess for vertebral fractures or scoliosis, and an MRI if neurological symptoms appear. Early orthopedic referral can prevent permanent nerve damage.
Look for early‑onset bowing (often before age 2), short stature, and dental problems. Laboratory tests showing low serum phosphate, normal calcium, elevated alkaline phosphatase, and high FGF‑23 support the diagnosis. A skeletal X‑ray will reveal characteristic metaphyseal widening and fraying. If these findings are present, ask your pediatrician for genetic testing of the PHEX gene.
Standard therapy combines multiple daily doses of oral phosphate salts (usually 30–60 mg/kg/day divided 3–5 times) with active vitamin D analogs such as calcitriol (20–30 ng/kg/day). Newer therapy with the monoclonal antibody burosumab is given by subcutaneous injection every 2 weeks (or every 4 weeks in some protocols) and can reduce the need for high‑dose phosphate. Dosing is individualized and requires regular monitoring of serum phosphate, calcium, and urinary excretion.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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