ESPE Abstracts

Case description: A 14-year old boy with autoimmune hepatitis who was on long term oral steroids for 10 years, presented with acute onset lower back pain without preceding trauma. Lumbar spine radiograph showed severe osteopenia and compression fractures of vertebrae T12 to L1. Bone mineral density T-score at the lumbar region was −4.9. Biochemically, there was hypocalcaemia and severe hypophosphataemia with adjusted calcium 2.03 (2.20–2.65) mmol/l and phosphate 0.87 (1.18–1.89) mmol. Serum PTH levels were normal. Serum 25-hydroxy-vitamin-D3 was insufficient at 14.9 μg/l despite him being on daily cholecalciferol 1000 units for vitamin D deficiency from cholestasis-induced malabsorption. Urine phosphate levels were grossly elevated at 8.3 (1.29–1.94) mmol/l. Work up for renal tubular acidosis was negative. The patient was placed on calcium, phosphate and vitamin D replacements and treated with intravenous bisphosphonates. Despite supraphysiological doses of oral phosphate replacement at 3 mmol/kg per day, phosphate levels remained suboptimal at 0.8–0.9 mmol/l. High levels of fibroblast growth factor 23 (FGF23) at 840 (<230) RU/ml provided a clue to the etiology behind this new onset hypophosphataemia and hyperphosphaturia. As the high FGF23 could be from a paraneoplastic tumour secretion, the Ga68-DATONAC PET-CT was performed and was normal. The age of onset of the hypophosphataemia made hereditary hypophosphataemic rickets (HHR) an unlikely cause for this. The patient underwent a living-related liver transplant for end-stage liver disease (ESLD) 6 months later. Two months post-transplant, phosphate levels normalized and FGF23 levels dropped to 180 RU/ml. He was weaned off phosphate replacements and was able to maintain normal serum phosphate levels thereafter.

Discussion: FGF23 is a key regulator of phosphate homeostasis. It acts at the proximal renal collecting tubules to increase urine phosphate excretion and reduces 1,25-dihydroxyvitamin-D3 production. Elevated serum FGF23 occurs in HHR due to the PHEX gene mutation and in tumour-induced osteomalacia in children. High levels of FGF23 have been described in patients with cholestatic liver disease and ESLD. Elevated FGF23 mRNA re-expression has been demonstrated in hepatocytes of patients with ESLD. FGF23 levels are associated with an increased risk of mortality in an adult cohort with ESLD awaiting transplant.

Conclusions: High FGF23 levels should be considered in children with ESLD who develop severe osteoporosis. This condition requires treatment with high levels of phosphate and vitamin D replacements until eventual liver transplantation, which can provide a cure.