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Osteoporosis International

, Volume 30, Issue 2, pp 481–489 | Cite as

Mutation update and long-term outcome after treatment with active vitamin D3 in Chinese patients with pseudovitamin D-deficiency rickets (PDDR)

  • Y. Chi
  • J. Sun
  • L. Pang
  • R. Jiajue
  • Y. Jiang
  • O. Wang
  • M. Li
  • X. Xing
  • Y. Hu
  • X. Zhou
  • X. Meng
  • W. XiaEmail author
Original Article

Abstract

Summary

Pseudovitamin D-deficiency rickets is a rare disease which is caused by CYP27B1. In this study, we identified 9 mutations in 7 PDDR patients. In addition, we observed the response to long-term treatment of calcitriol in 15 Chinese patients with PDDR, which showed that the biochemical abnormalities had been corrected satisfactorily after 1-year treatment.

Introduction

Pseudovitamin D-deficiency rickets is a rare autosomal recessive disorder resulting from a defect in 25-hydroxyvitamin D 1α-hydroxylase, which is encoded by CYP27B1. The purpose of this study was to identify the CYP27B1 mutations and investigate the response to long-term treatment of calcitriol in Chinese patients with PDDR.

Methods

We investigated CYP27B1 mutations in seven individuals from six separate families. To investigate the response to long-term (13 years) treatment with calcitriol in PDDR patients, we additionally collected clinical data of eight families from our previous report and analyzed their biochemical parameter and radiographic changes during the treatment.

Results

Nine different mutations were identified: two novel missense mutations (G194R, R259L), three novel and one reported deletion mutations (c1442delA, c1504delA, c311-321del, and c. 48-60del), two novel nonsense mutations (c.85G>T, c.580G>T), and a reported insertion mutation (c1325-1332insCCCACCC). The statistical analysis revealed that parathyroid hormone (PTH) and ALP significantly decreased after 6-month and 1-year treatment with calcitriol respectively. Urine calcium was measured in all the patients without kidney stones being documented. After 6-year treatment, the radiographic abnormalities had also been improved. Two patients who had reached their final height are both with short stature (height Z-score below − 2.0).

Conclusions

We identified seven novel mutations of CYP27B1 gene in seven Chinese PDDR families. Our findings revealed after 1-year treatment of active vitamin D3, PTH and ALP significantly decreased. The correction of the biochemical abnormalities had not improved the final height satisfactorily.

Keywords

Calcitriol CYP27B1 Mutation Pseudovitamin D-deficiency rickets (PDDR) Treatment 

Notes

Acknowledgments

We appreciate our patients and their families for their participating in this study.

Funding information

This study was supported by a grant from The Ministry of Science and Technology of the Peoples Republic of China (National Science and Technology Major Projects for Major New Drugs Innovation and Development 2008ZX09312-016), National Natural Science Foundation of China (No. 81070687, 81170805, and 81670714), Beijing Natural Science Foundation (No. 7121012) and Scientific Research Foundation of Beijing Medical Development (No. 2007-3029), National Key Program of Clinical Science (WBYZ2011-873), and CAMS Innovation Fund for Medical Sciences (No. 2016-I2M-3-003).

Compliance with ethical standards

This study was approved by the Department of Scientific Research at Peking Union Medical College Hospital. Written informed consent was obtained from the patients and their family members included in this study.

Conflicts of interest

None.

Supplementary material

198_2018_4607_MOESM1_ESM.doc (34 kb)
ESM 1 (DOC 33 kb)

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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2018

Authors and Affiliations

  1. 1.Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijingChina

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