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

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

Affiliations

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

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

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

Abstract and keywords

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.

Keywords: Autosomal dominant hypophosphatemic rickets; Fibroblast growth factor 23; Iron deficiency; Phosphate

Links

DOI: 10.1007/s00198-020-05649-w

PubMed: 32995940

WoS: 000573797000001

History

Received: 2020-07-04

Accepted: 2020-09-17

Online: 2020-09-30

Cited Works (4)

Year	Entry
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Cited By (1)

Year	Entry
2023	Liu C, Ni X, Zhao Z, Qi W, Jiang Y, Li M, Wang O, Xing X, Xia W. Bone characteristics of autosomal dominant hypophosphatemic rickets patients. Bone. February 2023;167:116602.