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Osteoporosis International

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01-02-2019 | Original Article

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

Authors: Y. Chi, J. Sun, L. Pang, R. Jiajue, Y. Jiang, O. Wang, M. Li, X. Xing, Y. Hu, X. Zhou, X. Meng, W. Xia

Published in: Osteoporosis International | Issue 2/2019

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.

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Title: Mutation update and long-term outcome after treatment with active vitamin D3 in Chinese patients with pseudovitamin D-deficiency rickets (PDDR)
Authors: Y. Chi
J. Sun
L. Pang
R. Jiajue
Y. Jiang
O. Wang
M. Li
X. Xing
Y. Hu
X. Zhou
X. Meng
W. Xia
Publication date: 01-02-2019
Publisher: Springer London
Published in: Osteoporosis International / Issue 2/2019
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-018-4607-5

At a glance: The STEP trials

Springer Medicine

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

Abstract

Summary

Introduction

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusions

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