ESPE Abstracts

Objective: Hereditary hypophosphatemic rickets is a rare renal phosphate wasting disorder causing burden on pediatric patients despite conventional treatment of phosphate and calcitriol. The aim of this study is to analyze genetic and clinical variability of children with X-linked hypophosphatemic rickets (XLHR), focusing on short term, long term and pubertal impact of conventional treatment. Design: Retrospective cohort study

Methods: Mutation analysis of PHEX was performed in 16 patients from 12 unrelated families with HR via Sanger sequencing first than multiplex ligand-dependent probe amplification. If a molecular defect was detected, first-degree relatives were analyzed. 13 patients (81%) and five first-degree relatives with XLHR were analyzed to determine the correlation between phenotype with genotype or gender. In addition, clinical characteristics and response to conventional treatment were determined retrospectively.

Results: Nine different PHEX mutations were identified, four were novel. Four led to disrupted splice-site, three were point mutations, and two were single exon deletions. In XLHR, despite conventional treatment, median adult height was lower than median height on admission (-3.8 and -2.3 SDS; respectively), metabolic and radiographic recovery were not achieved, adherence was low (30%). Although mean adult height was better in compliant patients than noncompliant ones (-2.6 vs -3.7 SDS; respectively), they were shorter than their peers. A correlation between phenotype and genotype or gender could not be shown. Median phosphate decreased significantly throughout puberty (P = 0.014). Median pubertal height (-4.4 SDS) was lower than that of prepubertal height (-3.6 SDS) and pubertal growth spurt was not observed. In the long term, nephrocalcinosis (60%) and hyperparathyroidism (40%) were observed, correction osteotomy (33%) was required.

Conclusion: Metabolic, clinical and radiographic recovery were not achieved owing to limited benefits of conventional treatment. In addition, response to treatment worsened during puberty. Thus, introduction of monoclonal FGF-23 antibody as first-line treatment may be an alternative after infancy. However, long-term adverse effects are yet to be seen.