A Case of Vitamin-D-Dependent Rickets Type 1A with Normal 1,25-Dihydroxyvitamin D Caused by Two Novel Mutations of the CYP27B1 Gene

作者：Giannakopoulos Aris^*; Efthymiadou Alexandra; Chrysis Dionisios

来源：Hormone Research in Paediatrics, 2017, 87(1): 58-63.

DOI：10.1159/000446774

• Rickets
• Vitamin-D-dependent rickets
• CYP27B1 gene

Background: Vitamin-D-dependent rickets 1A (VDDR-1A) is caused by mutations of the renal CYP27B1 gene and is a rare form of rickets. Herein, we report a 20-month-old toddler who presented with inability to walk and failure to thrive. The clinical, biochemical and radiological findings were consistent with a diagnosis of rickets, specifically of the genetic type due to increased 25-OH vitamin D stores. Methods and Results: Our patient was a compound heterozygote with 2 novel mutations: c.242G>A(p.Gly81Glu) and c.1144C>G (p.Pro382Ala) in the CYP27B1 gene. Analysis of both mutations with in silico models predicted a deleterious effect on 25-OH vitamin D 1 alpha-hydroxylase function. Interestingly, the levels of 1,25-(OH)(2) vitamin D were within normal limits. Our patient was initiated on 1 alpha-hydroxyvitamin D (alfacalcidol) and supplemental calcium. Monitoring of bone metabolism showed a normalization of all bone metabolism serum indices after 3 months of therapy and, thereafter, only alfacalcidol was given at a maintenance dose. The clinical follow-up showed a dramatic improvement in musculoskeletal activity, and the patient regained acceleration in height and weight appropriate for his age. Conclusion: This rare case report of VDDR-1A with normal levels of 1,25-(OH)(2) vitamin D enhances our awareness for this type of rickets in clinical practice.

• 出版日期2017