Growth hormone therapy in HHRH

Guido Filler; Clara Schott; Fabio Rosario Salerno; Andrea Ens; Christopher William McIntyre; Maria Esther Díaz González de Ferris; Robert Stein

doi:10.1016/j.bonr.2022.101591

Growth hormone therapy in HHRH

Bone Rep. 2022 May 18:16:101591. doi: 10.1016/j.bonr.2022.101591. eCollection 2022 Jun.

Authors

Guido Filler^{1

2

3

4}, Clara Schott⁵, Fabio Rosario Salerno^{6

4}, Andrea Ens¹, Christopher William McIntyre^{1

2

6

4}, Maria Esther Díaz González de Ferris⁷, Robert Stein¹

Affiliations

¹ Departments of Pediatrics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Canada.
² Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Canada.
³ Pathology & Laboratory Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Canada.
⁴ Lilibeth Caberto Kidney Clinical Research Unit, London, Ontario, Canada.
⁵ Medical Sciences, University of Western Ontario, Canada.
⁶ Biophysics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Canada.
⁷ University of North Carolina at Chapel Hill, Department of Pediatrics, Chapel Hill, NC, USA.

Abstract

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[<0.6]). TmP/GFR was 0.65 mmol/L[0.97-1.64]; 1,25(OH)₂D 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)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.

Keywords: 23Na MRI; Hereditary hypophosphatemic rickets with hypercalciuria; Recombinant human growth hormone; Sodium phosphate cotransporter; Tubular phosphate wasting.

Publication types

Case Reports