Growth hormone therapy in HHRH()

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)(2)D) levels or short stature. METHODS: We describe (23)Na 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[<0.6]). TmP/GFR was 0.65 mmol/L[0.97–1.64]; 1,25(OH)(2)D was >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)(2)D to 462 and 426 pmol/L; serum phosphate 0.87 mmol/L, and calcium/creatinine ratio of 0.73. (23)Na 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.