X linked Hypophosphataemic rickets
๐งฌ X-linked hypophosphataemic rickets (XLH) is the most common inherited form of rickets. It results in chronic phosphate wasting, defective bone mineralisation, and osteomalacia in adults.
- Caused by renal phosphate wasting due to abnormal FGF23/PHEX signalling.
- Presents as rickets in children and osteomalacia in adults.
- Distinguished from nutritional rickets by normal calcium and normal/raised vitamin D, but low phosphate.
๐งฌ Aetiology
- PHEX mutation (Xp22.1): most common, inherited in an X-linked dominant pattern.
- FGF23 mutation: leads to excess FGF23 activity, reducing renal phosphate reabsorption and inhibiting 1-ฮฑ hydroxylase.
- Other forms:
- Autosomal dominant hypophosphataemic rickets (ADHR)
- Tumour-induced osteomalacia (acquired, FGF23-secreting mesenchymal tumours) โ CT TAP often needed for localisation.
๐ฉบ Clinical Features
- Usually childhood onset:
- Short stature, growth delay ๐
- Lower limb deformities (genu varum, knock knees)
- Bone pain, proximal myopathy
- In adults: bone pain, fractures, enthesopathy, osteoarthritis
๐ Investigations
- Bloods:
- โ Serum phosphate (hallmark)
- Normal/low serum calcium
- โ Alkaline phosphatase (ALP)
- โ Parathyroid hormone (secondary hyperparathyroidism)
- 25(OH) vitamin D usually normal, but โ 1,25(OH)โ vitamin D
- Urine: Phosphate wasting (low TmP/GFR).
- Imaging: CT/MRI if malignancy suspected (tumour-induced osteomalacia).
๐ Management
- ๐ถ In children: early treatment prevents growth impairment and skeletal deformities.
- Oral phosphate supplements (divided doses).
- Active vitamin D analogues: Calcitriol or alfacalcidol to enhance intestinal phosphate absorption and bone mineralisation.
- New therapies: Burosumab (anti-FGF23 monoclonal antibody) is approved for XLH and tumour-induced osteomalacia, with promising results.
- Correct dental disease and deformities; orthopaedic input may be needed.
Exam Tip
๐ XLH = Low phosphate + Normal calcium + High ALP.
Differentiate from nutritional rickets (low calcium, low vitamin D) and renal failure (raised phosphate).
