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Objectives: To explore the clinical value of the renal phosphorus threshold (ratio of tubular maximum reabsorption of phosphate to glomerular filtration rate, TmP/GFR) in the diagnosis and treatment of children with X-linked hypophosphatemic rickets (XLH)., Methods: A retrospective study was conducted, including 83 children diagnosed with XLH at Children's Hospital of Nanjing Medical University from January 2010 to January 2023. Initial diagnosis and follow-up data were collected to investigate the correlation of TmP/GFR with the severity of rickets, calcium and phosphorus metabolism indicators, and the dosage of phosphate treatment. Children were divided into two groups based on the occurrence of renal calcification: the renal calcification group ( n =47) and the non-renal calcification group ( n =36). Clinical data between the two groups were compared. Multivariate logistic regression analysis was used to identify factors influencing renal calcification in XLH children. The predictive value of TmP/GFR for renal calcification in XLH children was evaluated using receiver operating characteristic (ROC) curves., Results: In the 83 XLH children, the initial TmP/GFR was (0.78±0.21) mmol/L, with significant individual variation (range: 0.28-1.24 mmol/L). TmP/GFR showed no significant correlation with the severity of rickets ( P >0.05). Parathyroid hormone was negatively correlated with TmP/GFR ( r s =-0.020, P =0.008), while blood phosphorus ( r s =0.384, P <0.001), blood calcium ( r s =0.251, P <0.001), and 25-hydroxyvitamin D ( r s =0.179, P <0.001) were positively correlated with TmP/GFR. No significant correlation was found between TmP/GFR and alkaline phosphatase ( r s =-0.002, P =0.960) or phosphate treatment dosage ( r s =0.012, P =0.800). Blood calcium and TmP/GFR levels were significantly lower in the renal calcification group than in the non-renal calcification group ( P <0.05), while parathyroid hormone and urine calcium levels were significantly higher in the renal calcification group ( P <0.05). Multivariate logistic regression analysis indicated that TmP/GFR and urine calcium levels were closely associated with renal calcification in XLH children ( P <0.05). ROC curve analysis revealed that the areas under the curve for TmP/GFR, urine calcium, and their combined detection predicting renal calcification in XLH children were 0.696, 0.679, and 0.761, respectively., Conclusions: TmP/GFR may serve as an important diagnostic indicator for pediatric XLH; however, it does not reflect the severity or activity of rickets and cannot be used to judge the efficacy of traditional treatment. Urine calcium and TmP/GFR are valuable predictors for renal calcification in XLH children.

Objectives: To study the value of serum fibroblast growth factor 23 (FGF23) in the diagnosis of hypophosphatemic rickets in children., Methods: A total of 28 children who were diagnosed with hypophosphatemic rickets in Children's Hospital of Nanjing Medical University from January 2016 to June 2021 were included as the rickets group. Forty healthy children, matched for sex and age, who attended the Department of Child Healthcare of the hospital were included as the healthy control group. The serum level of FGF23 was compared between the two groups, and the correlations of the serum FGF23 level with clinical characteristics and laboratory test results were analyzed. The value of serum FGF23 in the diagnosis of hypophosphatemic rickets was assessed., Results: The rickets group had a significantly higher serum level of FGF23 than the healthy control group ( P <0.05). In the rickets group, the serum FGF23 level was positively correlated with the serum alkaline phosphatase level ( r s =0.38, P <0.05) and was negatively correlated with maximum renal tubular phosphorus uptake/glomerular filtration rate ( r s =-0.64, P <0.05), while it was not correlated with age, height Z-score, sex, and parathyroid hormone ( P >0.05). Serum FGF23 had a sensitivity of 0.821, a specificity of 0.925, an optimal cut-off value of 55.77 pg/mL, and an area under the curve of 0.874 in the diagnosis of hypophosphatemic rickets ( P <0.05)., Conclusions: Serum FGF23 is of valuable in the diagnosis of hypophosphatemic rickets in children, which providing a theoretical basis for early diagnosis of this disease in clinical practice.

Objective: To explore the clinical characteristics and genetic mutation in a family affected with hypophosphatemic rickets., Methods: Whole exome sequencing (WES) was used to screen potential mutations in genomic DNA extracted from peripheral venous blood sample from the proband. Suspected mutation was confirmed with Sanger sequencing. Amniotic fluid was sampled from the proband for prenatal diagnosis. Potential maternal contamination was excluded by analysis of short tandem repeat (STR) markers., Results: WES has identified a heterozygous c.2058&#95;2059insAGTT (p.L686fs) mutation of the PHEX gene in the proband, which was confirmed by Sanger sequencing in other affected individuals from the family. The mutation was detected in the amniotic fluid sample from the fetus but not among healthy members from the family., Conclusion: Identification of the PHEX mutation by WES has facilitated genetic counseling and prenatal diagnosis for the family affected with hypophosphatemic rickets.