Vitamin D resistant rickets (Children)
Related Subjects:
|Vitamin D Replacement
|Osteomalacia-Rickets-Vitamin D
|Vitamin D resistant rickets
|Vitamin D (25 OH D) Testing
|X linked Hypophosphataemic rickets
|Osteoporosis
🦴 In Hypophosphatemic Rickets, defective renal phosphate reabsorption causes chronic phosphate wasting and hypophosphatemia. Unlike nutritional rickets, patients typically do not respond to standard Vitamin D therapy.
📖 About
- Hypophosphatemic Rickets (also called Vitamin D–Resistant Rickets) is a disorder of mineral metabolism caused by renal phosphate wasting.
- Inheritance is most commonly X-linked dominant (mutation in the PHEX gene). Autosomal recessive and sporadic forms exist.
- Most patients present in childhood with rickets that fails to improve despite Vitamin D supplementation.
🧬 Renal Tubular (RT) Forms
- Type I: Defect in renal 1-alpha-hydroxylase, leading to inadequate conversion of 25(OH)D → 1,25(OH)2D.
- Type II: End-organ resistance to active Vitamin D (1,25(OH)2D).
- Both are treated with high doses of calcitriol (active Vitamin D).
⚙️ Aetiology & Pathophysiology
- 🧪 Defective phosphate reabsorption in the proximal renal tubules → urinary phosphate wasting.
- ⬇️ Serum phosphate → impaired bone mineralisation → rickets/osteomalacia.
- Frequently associated with elevated FGF23 (fibroblast growth factor-23), a hormone that suppresses phosphate reabsorption and 1-alpha-hydroxylase activity.
🩺 Clinical Features
- 👶 Presents in infancy or early childhood.
- 📏 Short stature & growth failure.
- 🦵 Bowed legs (genu varum) or knock knees (genu valgum).
- 🦷 Dental problems: delayed dentition, spontaneous abscesses.
- Other possible features:
- 👂 Deafness
- 🧠 Chiari malformation
- 💀 Craniosynostosis
- 🪨 Calcification of ligaments, tendons, and joint capsules
- 🪥 Renal stones or nephrocalcinosis
🔎 Investigations
- ⬇️ Serum phosphate
- ⬆️ Alkaline phosphatase (ALP)
- ⬆️ Urinary phosphate excretion
- ⬇️ or normal calcium
- ⬆️ Parathyroid hormone (secondary hyperparathyroidism)
- Normal 25(OH)D but impaired 1,25(OH)2D
- Renal USS: may reveal nephrocalcinosis or stones
- Genetic testing for PHEX mutation in suspected familial cases
⚕️ Management
- 💊 Oral phosphate supplements (divided doses to minimise GI upset).
- 💊 Calcitriol or alfacalcidol (active Vitamin D) to bypass renal conversion defects.
- 🧬 Burosumab (anti-FGF23 monoclonal antibody): NICE-approved for X-linked hypophosphatemia, improves phosphate reabsorption and bone health.
- 📈 Growth hormone therapy in selected cases with severe growth retardation.
- 💧 Amiloride or thiazides: may help reduce calcium excretion and prevent nephrocalcinosis.
- 🦴 Supportive: orthopaedic surgery for severe deformities, dental surveillance.
💡 Exam Pearls
- 🧪 Distinguish from nutritional rickets: here, Vitamin D is normal but phosphate is low.
- 🧬 X-linked dominant inheritance – fathers cannot pass to sons, but all daughters are affected.
- 🦵 Persistent bowed legs despite Vitamin D therapy is a red flag.
- 🌟 Burosumab is a game-changer in modern management.
📚 References
- NHS – Vitamin D Resistant Rickets
- Carpenter TO. X-linked hypophosphatemia. J Bone Miner Res. 2012;27(10):1983–1998.
- NICE Guidance (TA581): Burosumab for treating X-linked hypophosphataemia in children and young people.
