Maria Esther Díaz González de Ferris, MD, PhD, MPH,
Robert Stein, MD, MDCM
Affiliations
Guido Filler, MD, PhD
Departments of Pediatrics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Canada; Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Canada; Pathology & Laboratory Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Canada; Lilibeth Caberto Kidney Clinical Research Unit, London, Ontario, Canada; Corresponding author at: 800 Commissioners Road East, E3-206, University of Western Ontario, London N6A 5W9, Ontario, Canada.
Clara Schott
Medical Sciences, University of Western Ontario, Canada
Fabio Rosario Salerno, MD, PhD cand.
Biophysics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Canada; Lilibeth Caberto Kidney Clinical Research Unit, London, Ontario, Canada
Andrea Ens, MD
Departments of Pediatrics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Canada
Christopher William McIntyre, MD, PhD
Departments of Pediatrics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Canada; Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Canada; Biophysics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Canada; Lilibeth Caberto Kidney Clinical Research Unit, London, Ontario, Canada
Maria Esther Díaz González de Ferris, MD, PhD, MPH
University of North Carolina at Chapel Hill, Department of Pediatrics, Chapel Hill, NC, USA
Robert Stein, MD, MDCM
Departments of Pediatrics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Canada
Background: Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH) (SLC34A3 gene, OMIM 241530) is an autosomal recessive disorder that results in a loss of function of the sodium-phosphate NPT2c channel at the proximal tubule. Phosphate supplementation rarely improves serum phosphate, hypercalciuria, nephrocalcinosis, 1,25(OH)2 vitamin D (1,25(OH)2D) levels or short stature. Methods: We describe 23Na MRI and the successful use of recombinant human growth hormone (rhGH) and Fluconazole to improve growth (possibly confounded by puberty) and hypercalciuria in a now 12-year-old male with HHRH (novel homozygous SLC34A3 mutation, c.835_846 + 10del.T). Results: The patient had chronic bone pain, hypophosphatemia (0.65 mmol/L[reference interval 1.1–1.9]), pathological fractures and medullary nephrocalcinosis/hypercalciuria (urinary calcium/creatinine ratio 1.66 mol/mmol[480 pmol/L[60–208]. Rickets Severity Score was 4. Treatment with 65 mg/kg/day of sodium phosphate and potassium citrate 10 mmol TID failed to correct the abnormalities.Adding rhGH at 0.35 mg/kg/week to the phosphate therapy, improved bone pain, height z-score from −2.09 to −1.42 over 6 months, without a sustained effect on TmP/GFR. Fluconazole was titrated to 100 mg once daily, resulting for the first time in a reduction of the 1,25(OH)2D to 462 and 426 pmol/L; serum phosphate 0.87 mmol/L, and calcium/creatinine ratio of 0.73.23Na MRI showed normal skin (z-score + 0.68) and triceps surae muscle (z-score + 1.5) Na+ levels; despite a defect in a sodium transporter, hence providing a rationale for a low sodium diet to improve hypercalciuria. Conclusions: The addition of rhGH, Fluconazole and salt restriction to phosphate/potassium supplementation improved the conventional therapy. Larger studies are needed to confirm our findings.
