Nationwide Turkish Cohort Study of Hypophosphatemic Rickets

Area of Science:

• Nephrology
• Pediatric Endocrinology
• Genetics

Background:

• Hypophosphatemic rickets (HR) is a rare genetic disorder characterized by renal phosphate wasting.
• X-linked hypophosphatemia, often caused by PHEX mutations, presents treatment challenges due to limited therapeutic options.

Purpose of the Study:

• To present nationwide data on the initial treatment and long-term follow-up of hypophosphatemic rickets.
• To evaluate treatment efficacy and identify factors associated with outcomes and complications.

Main Methods:

• A nationwide cohort study included 166 patients with HR from 24 centers.
• Genetic analysis confirmed PHEX mutations in 80% of tested patients (n=75).
• Data collected included biochemical parameters, growth, skeletal deformities, and nephrocalcinosis over a mean follow-up of 6.7 years.

Main Results:

• Treatment over 3 years showed mild increases in phosphate, decreased alkaline phosphatase, and elevated parathyroid hormone (PTH) levels, with no significant improvement in height standard deviation scores.
• 36% of patients experienced improvement in leg deformities, with similar phosphate levels but better treatment-year levels compared to those without improvement.
• Nephrocalcinosis (NC) developed in 27 patients, associated with higher phosphate and calcitriol doses, and elevated 3rd-year PTH, despite similar baseline and follow-up biochemical profiles.

Conclusions:

• HR management is complex; higher phosphate and calcitriol doses correlate with NC, possibly via FGF23, without improving serum phosphate.
• Calcitriol may offer benefits for bone deformities in HR patients.
• Development of safer and more effective therapies for HR is crucial.