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Iron deficiency plays essential roles in the trigger, treatment, and prognosis of autosomal dominant hypophosphatemic rickets

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Abstract

Summary

By analyzing iron status of 14 ADHR patients, we found that iron deficiency was an important trigger of ADHR. Correcting iron deficiency significantly improved patients’ symptoms. Meanwhile, patients’ serum phosphate showed positive correlations with iron metabolism parameters and hemoglobin-related parameters, suggesting the necessity of monitoring and correcting the iron status in ADHR.

Introduction

Autosomal dominant hypophosphatemic rickets (ADHR) is unique for its incomplete penetrance, variety of disease onsets, and waxing and waning phenotypes. Iron deficiency is a trigger of ADHR. This study aimed to clarify the role of iron deficiency in ADHR.

Methods

Data of clinical manifestations and laboratory examinations were collected from patients among eight kindreds with ADHR. Multiple regression and Pearson’s correlation tests were performed to test the relationships of serum phosphate levels and other laboratory variables during the patients’ follow-ups.

Results

Among 23 ADHR patients with fibroblast growth factor 23 (FGF23) mutations, 14 patients presented with obvious symptoms. Ten patients had iron deficiency at the onset of ADHR, coinciding with menarche, menorrhagia, pregnancy, and chronic gastrointestinal bleeding. Two patients who did not have their iron status tested presented with symptoms after abortion and pregnancy in one patient each, which suggested that they also had iron deficiency at onset. Patients were treated with ferrous succinate tablets, vitamin C, and neutral phosphate and calcitriol. With correction of the iron status, the patients’ symptoms showed notable improvement, with increased serum phosphate levels. Two patients’ FGF23 levels also declined to the normal range. There were strong correlations between serum phosphate and serum iron levels (r = 0.7689, p < 0.0001), serum ferritin levels (r = 0.5312, p = 0.002), iron saturation (r = 0.7907, p < 0.0001), and transferrin saturation (r = 0.7875, p < 0.001). We also examined the relationships between serum phosphate levels and hemoglobin-related indices, which were significant (hemoglobin: r = 0.71, p < 0.0001; MCV: r = 0.7589, p < 0.0001; MCH: r = 0.8218, p < 0.0001; and MCHC: r = 0.7751, p < 0.0001). Longitudinal data of six patients’ follow-up also showed synchronous changes in serum phosphate with serum iron levels.

Conclusions

Iron deficiency plays an important role in triggering ADHR. Monitoring and correcting the iron status are helpful for diagnosing and treating ADHR. Iron metabolism parameters and hemoglobin-related parameters are positively correlated with serum phosphate levels in patients with ADHR and iron deficiency, and these might serve as good indicators of prognosis of ADHR.

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Acknowledgments

We appreciate our patients and their family for their participation in this study.

Funding

This study was supported by a grant from the National Natural Science Foundation of China (Nos. 81970757 and 81670714), National Key Program of Clinical Science (WBYZ2011-873), and the CAMS Innovation Fund for Medical Sciences (No. 2016-I2M-3-003).

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Authors and Affiliations

  1. Department of Endocrinology, NHC Key Laboratory of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China

    C. Liu, X. Li, Z. Zhao, Y. Chi, L. Cui, Q. Zhang, F. Ping, X. Chai, Y. Jiang, O. Wang, M. Li, X. Xing & W. Xia

  2. Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China

    Z. Zhao

  3. Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China

    Q. Zhang

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  1. C. Liu
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Correspondence to W. Xia.

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Our study was approved by the Institutional Review Boards of Peking Union Medical College Hospital (PUMCH). Written informed consent was obtained from all subjects.

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Liu, C., Li, X., Zhao, Z. et al. Iron deficiency plays essential roles in the trigger, treatment, and prognosis of autosomal dominant hypophosphatemic rickets. Osteoporos Int 32, 737–745 (2021). https://doi.org/10.1007/s00198-020-05649-w

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