Objectives: X-linked hypophosphatemic Rickets (XLHR) is characterized by phosphate wasting and decreased production of 1,25OH-vitamin D, due, in most patients, to elevated FGF23 and PHEX mutation. In children, the disease has been extensively studied because of the devastating presentation of rickets, teeth abcesses, and growth retardation. In adults, however, metabolic complications, such as hyperparathyroidism or consequences on glucose and lipid metabolism of FGF23 excess, have never been prospectively investigated.
Patients: Consecutive patients (35 years (2148), 14F/6M), affected with XLHR and PHEX mutation, have been investigated 3 months after stopping their treatment (phosphate supplements and vitamin D analogues).
Results: As expected, patients presented with low serum phosphate (0.58 mmol/l, 0.340.88), elevated urinary phosphate (24 mmol/24 h, 1652) and unadapted FGF23 (108 RUI/l, 60387). Parathyroid function was found normal in 19/20 patients (calcemia: 2.29 mmol/l, 2.102.44; PTH: 33 pg/ml, 1774; 25-OHvitamin D: 25 ng/ml, 1444; calcitriol 54 ng/ml, 28120; calciuria: 2.67 mmol/24 h, 0.946.63). Parathyroid scintigraphies and renal ultrasounds were normal in these patients. One patient was diagnosed with hyperparathyroidism.
Eleven patients were overweight or obese (BMI 25.6 kg/m2, 20.942.2); one patient met the criteria for glucose intolerance on OGTT; five patients had abnormal lipid profiles.
Conclusion: Long-term consequences of phosphate wasting and calcitriol insufficiency, as well as metabolic consequences of FGF23 excess need to be evaluated. Tertiary hyperparathyroidism or renal impairment are not frequent. However, XLHR patients appear at increased risk of metabolic syndrome. The respective contributions of FGF23 and decreased physical activity remain to be determined.