ESPE Abstracts

The measurement of serum FGF23 plays a pivotal role in the differential diagnosis of patients with hypophosphatemia. However, its interpretation may be difficult in some cases. We report the case of a child with rickets and severe hypophosphatemia, where both intact FGF23 (iFGF23), the active form, and C terminal FGF23 fragments (C-FGF23) were measured.

Case report: A 5.7-year-old girl, born at term from first-grade-related Pakistani parents, was referred to our pediatric endocrinology unit for poor growth. She showed short stature (-2.52SDS), poor trophism (weight -2.35 SDS) and mild signs of rickets (wrist bracelets, rachitic rosary, mild genu valgum, prognathism) with slow, wide-based gait. She suffered a traumatic greenstick fracture of the right tibia two months before. Blood test showed: Hb 11.8 g/dL, severe hypophosphatemia (1.3 mg/dl), normal total calcium (9.4 mg/dl), elevated PTH (374 pg/ml), undetectable vitamin 25(OH) D, TmP04/GFR consistently reduced (1.38 mg/dl) Bone age was four years and metaphyseal widening and cupping were evident. To rule out FGF23-dependent hypophosphatemic rickets, iFGF23 and C-fragments serum levels were requested. In the meantime, cholecalciferol (3000 IU/day) and Calcium carbonate (500 mg/day) were started. iFGF23 levels resulted in a normal range (70.9 pg/ml; nr 23-95) with elevated C-FGF23 fragments (> 150; nr <9.8). After 12 weeks, the treatment with calcium carbonate was interrupted. Due to early and progressive serum phosphate amelioration, the patients only continued cholecalciferol treatment. After six months of therapy, growth and clinical picture consistently improved, PTH became normal (60 pg/ml), as well as phosphate level (5.4 mg/dl); TmP/GFR (4.2 mg/dl) also showed progressive improvement. After nine months, iFGF23 and C-FGF23 fragments were re-evaluated showing normal values (79.6 pg/ml and 9.5 pg/ml respectively). The final diagnosis was severe nutritional rickets.

Discussion: In our case, we argued that unsuppressed levels of iFGF23 despite severe hypophosphatemia, could have been related to marked secondary hyperparathyroidism and probably elevated 1,25 (OH) D. We cannot exclude that elevated C-FGF23 fragments could be related to other factors as iron deficiency or represent a tentative to alleviate hypophosphatemia. The persistently low TmP/GFR is likely due to the poor availability of phosphate for renal excretion.

Conclusion: Severe vitamin D deficiency should be ruled out in all children with rickets, even with severe hypophosphatemia with elevated PTH. In these cases, FGF23 levels should be cautiously interpreted and reevaluated after correcting vitamin D status.