Background: Hypophosphatemic rickets (HR) comprises a group of inherited forms of rickets characterised by renal phosphate wasting. Taking info account the latest advances in HR therapy, it now becomes of interest to better define the mutational and phenotypic spectra of disease.
Objective and Hypotheses: The aim of this study was to clinically characterize and perform genetic analysis of 168 cases with HR.
Method: 168 patients (aged from 1 month to 56 years; female, n=111; male, n=57) with clinical and radiological sings of rickets, low serum phosphate and low tubular reabsorption of phosphate were included in the study. There were 52 familial and 116 sporadic cases from 137 families. The method of Thacher was used to evaluate a Rickets Severity Score (RSS). 'Rickets panel' genes were sequenced using a custom Ion Ampliseq gene panel and PGM semiconductor sequencer (Ion Torrent). Bioinformatic analysis was performed using Torrent Suite (Ion Torrent) and ANNOVAR (annovar.openbioinformatics.org) software packages.
Results: The mean age at diagnosis was 7.5 years (aged from 2 month to 17 years). Clinical symptoms of HR included deformities of leg bones (90%), muscle weakness (75%), multiple dental abscesses (72%). The mean height SDS was −2.34±1.8, with 62.7% of patients less than −2 SD (n=144). 10 children that were diagnosed with HR and started treatment before the age of 2 had mean height SDS=−1.2±0.3 and mild leg deformities.The mean RSS was 4.5 points (range 1.510) (n=25). Mutations were identified in 92.3% of familial and 84.4% of sporadic cases. In 143 probands mutations were detected in PHEX, 70 of which were novel. Mutations were also detected in other genes: FGF23 (n=1), SLC34A3 (n=1) and CLCN5 (n=1).
Conclusion: This study showed the predominance of PHEX mutations among the patients with HR in Russia. We identified 117 PHEX mutations, including 70 unreported ones. Earlier diagnostic and treatment can result in less severe complications and improve the quality of life of patients with HR.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology