Mutation update and long-term outcome after treatment with active vitamin D3 in Chinese patients with pseudovitamin D-deficiency rickets (PDDR)
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.
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.
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.
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).
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.
KeywordsCalcitriol CYP27B1 Mutation Pseudovitamin D-deficiency rickets (PDDR) Treatment
We appreciate our patients and their families for their participating in this study.
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
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