Treatment of Rickets in Hereditary Hypophosphatemic Rickets with Hypercalciuria (SLC34A3 Mutation)
Clinical Scenario
This protocol covers Rickets in patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH) — a condition arising from mutations in SLC34A3 that cause loss of function of NaPi2c in the proximal tubule, resulting in renal phosphate wasting and characteristically elevated 1,25(OH)₂D levels.
Key Clinical Features
The NaPi2c transporter defect drives renal phosphate wasting. Unlike other hypophosphatemic disorders, HHRH is distinguished by elevated — not suppressed — 1,25(OH)₂D levels, alongside hypercalciuria. This biochemical profile is central to treatment selection in this condition.
Treatment Approach (Partial Overview)
The approach centres on oral phosphate supplementation. A defining feature of this condition's management is that treatment with active vitamin D is not indicated — a departure from other forms of hypophosphatemic rickets — given the already elevated 1,25(OH)₂D levels. Additional structured measures are specified in the full protocol…
Treatment Goals
- Normalization of serum phosphate
- Normalization of 1,25(OH)₂D concentrations
- Normalization of alkaline phosphatase
- Radiological improvement of rickets
References
- This condition is due to mutations in SLC34A3 resulting in loss of function of NaPi2c in the proximal tubule and consequent renal phosphate wasting.
- Patients with HHRH are treated with renal phosphate salts only.
- Treatment with active vitamin D is not indicated in view of the already elevated 1,25(OH)₂D levels.
- Primary target parameters on high phosphate supplementation are to normalize serum phosphate and 1,25(OH)₂D concentrations.
- Observational studies showed that treatment with phosphate supplements normalizes ALP and radiological surrogates of rickets in HHRH patients.
DOI: 10.1007/s00467-022-05505-5
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