Rickets, elevated fibroblast growth factor-23 and mild anemia: Answers

Abstract

Rickets is a disease of the pediatric skeleton caused by its under-mineralization secondary to hypophosphatemia [1]. The latter can be driven by insufficient intake of the mineral or due to its increased losses in the proximal tubule secondary to either elevated PTH, elevated FGF23, or isolated perturbations in the tubular reabsorption mechanisms [2]. The child’s normal serum PTH, 25(OH)-vitamin D, and urine calcium excretion, combined with low TP/GFR and relatively low 1,25(OH)2-vitamin D level, were consistent with the finding of hypophosphatemic rickets due to high FGF23 level. Thus, we focused our search for etiology on conditions associated with elevated levels of FGF23 [3]. Elevated serum FGF23 level is commonly seen as part of paraneoplastic syndrome in tumorinduced osteomalacia in adults but has been rarely described in children [4]. As there was no evidence in our patient for this acquired condition, the evaluation proceeded for a search of a genetic etiology. The most common condition is X-linked dominant familial hypophosphatemic rickets characterized by mutations in the PHEX gene [2, 5, 6]. Other less frequent genetic mutations causing hypophosphatemic rickets are autosomal dominant hypophosphatemic rickets (ADHR) from mutation in the FGF23 gene, autosomal recessive hypophosphatemic rickets (ARHR) from DMP1 or ENPP1 gene mutation, polyostotic fibrous dysplasia from GNAS1 gene mutation, or epidermal nevus syndrome from FGFR3 gene mutation [5]. The presence of normal PTH excluded mutation in Klotho gene and absence of dysmorphic clinical features excluded polyostotic fibrous dysplasia and epidermal nevus syndrome. Therefore, by process of elimination, our patient had either an autosomal recessive or dominant form of hypophosphatemic rickets.