What Is Vitamin D Resistant Rickets?

Vitamin D resistant rickets (VDRR), also known as hereditary hypophosphatemic rickets, is a rare genetic disorder in which the body cannot properly process and retain phosphate. Phosphate is critical for healthy bone formation and growth. Unlike more common forms of rickets caused by vitamin D deficiency, VDRR does not respond to standard vitamin D supplements alone. Early recognition and treatment can help manage symptoms and improve quality of life.

Types and Causes

There are several inherited forms of vitamin D resistant rickets, each caused by specific gene mutations:

• X-linked hypophosphatemia (XLH)
  • Most common form (approximately 1 in 20,000 births)
  • Mutation in the PHEX gene leads to excess fibroblast growth factor 23 (FGF23), which causes phosphate loss in urine
• Autosomal dominant hypophosphatemic rickets (ADHR)
  • Caused by mutations in the FGF23 gene itself
  • Symptoms may fluctuate over time, sometimes improving after puberty
• Autosomal recessive hypophosphatemia (ARHR)
  • Two different gene mutations (DMP1 or ENPP1) can lead to phosphate wasting
  • Often more severe bone and dental problems

In all forms, the result is low blood phosphate levels (hypophosphatemia) despite normal or even elevated levels of vitamin D metabolites.

How Phosphate and Bone Health Are Linked

• Phosphate combines with calcium to form hydroxyapatite, the mineral that gives bones their strength and structure.
• When phosphate levels remain too low, bones become soft, leading to rickets in children (bone deformities) and osteomalacia in adults (bone pain and weakness).
• In VDRR, the kidneys leak phosphate into the urine instead of reabsorbing it, so simply giving vitamin D does not correct the underlying phosphate loss.

Common Signs and Symptoms

Vitamin D resistant rickets can present in early childhood or sometimes later. Key symptoms include:

• Skeletal abnormalities
  • Bowed or curved legs (genu varum)
  • Knock-knees (genu valgum)
  • Widened wrists or ankles
  • Delayed closure of fontanelles (soft spots on an infant’s skull)
• Growth and development
  • Short stature or slowed growth rate
  • Delayed motor milestones (walking, running)
• Bone pain and muscle weakness
  • Complaints of leg or joint pain, especially after activity
  • Fatigue and difficulty climbing stairs
• Dental issues
  • Spontaneous dental abscesses
  • Defective enamel or dentin leading to cavities
• Other possible features
  • Hearing loss (in some forms)
  • Enthesopathy (calcification at tendon or ligament attachment sites)

If your child has persistent bone pain, deformities, or growth delays, consider a free, online symptom check, using the doctor approved Ubie Symptom Checker.

Diagnosis

Diagnosing vitamin D resistant rickets involves a combination of clinical evaluation, laboratory tests, imaging studies, and often genetic testing:

1. Blood tests
   • Low serum phosphate
   • Normal to low calcium
   • Elevated alkaline phosphatase (ALP)
   • Normal 25-hydroxyvitamin D and sometimes elevated 1,25-dihydroxyvitamin D
   • Elevated FGF23 levels (in some specialized labs)
2. Urine tests
   • High phosphate excretion (fractional excretion of phosphate)
3. Imaging
   • X-rays of wrists, knees, and legs show characteristic rickets changes (cupping and fraying of growth plates)
4. Genetic testing
   • Confirms the specific mutation (PHEX, FGF23, DMP1, ENPP1, etc.)
   • Helps predict inheritance patterns and guide family counseling

Early diagnosis is crucial, as untreated VDRR can lead to worsening bone deformities, chronic pain, and impaired growth.

Treatment Strategies

While vitamin D resistant rickets does not respond to standard vitamin D alone, current treatments aim to correct phosphate levels and support bone health:

• Oral phosphate supplements
– Multiple daily doses of phosphate salts (sodium or potassium phosphate)
– Requires close monitoring to avoid gastrointestinal upset and ensure proper dosing
• Active vitamin D analogs (calcitriol or alfacalcidol)
– Enhance intestinal phosphate and calcium absorption
– Help suppress secondary hyperparathyroidism (overactive parathyroid glands)
• Burosumab (Crysvita)
– A monoclonal antibody targeting excess FGF23
– Approved for XLH in children and adults
– Shown to raise phosphate levels, improve bone lesions, reduce pain, and enhance growth in children
• Orthopedic interventions
– Surgery to correct severe bone deformities (osteotomies, guided growth procedures)
– Physiotherapy to improve muscle strength and mobility

Treatment is lifelong in most cases. Regular follow-up appointments with a pediatric endocrinologist or metabolic bone specialist are essential to monitor growth, lab values, and potential side effects.

Monitoring and Lifestyle

• Routine blood and urine tests every 3–6 months (or as directed)
• Dental care: frequent check-ups to manage enamel defects and prevent abscesses
• Nutrition: balanced diet rich in calcium and phosphate (where not contraindicated)
• Physical activity: low-impact exercises to strengthen muscles without overloading bones
• Psychosocial support: connecting with support groups or counseling for chronic disease management

Prognosis

With timely and appropriate therapy, many children with vitamin D resistant rickets:

• Achieve improved bone mineralization
• Experience reduced pain and fewer fractures
• Attain near-normal growth, though final height may remain slightly below average

Adults may continue to need treatment for bone pain, dental issues, or enthesopathy. Advances like burosumab have transformed long-term outcomes, but lifelong medical care remains important.

When to Seek Medical Advice

Although vitamin D resistant rickets is not typically life-threatening, complications can be serious if untreated. Contact a healthcare provider if you or your child experience:

• Severe bone pain or muscle weakness
• New or worsening limb deformities
• Growth that falls significantly off normal percentiles
• Signs of secondary complications (kidney stones, hyperparathyroidism)

For an initial check of symptoms, consider a free, online symptom check, using the doctor approved Ubie Symptom Checker.

Always speak to a doctor about any concerns that could be life-threatening or require urgent attention.

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Vitamin D resistant rickets is a complex yet manageable condition. With early recognition, tailored therapy, and ongoing specialist care, individuals with VDRR can lead active, fulfilling lives. Regular monitoring, multidisciplinary support, and advances in treatment offer hope for improved bone health and well-being.