Clinical and genetic analysis of two Chinese families with vitamin D-dependent rickets type IA and follow-up
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RESEARCH
Clinical and genetic analysis of two Chinese families with vitamin D‑dependent rickets type IA and follow‑up Yunfei Li1,2†, Xin Yuan1†, Ruimin Chen1* , Xiangquan Lin1, Huakun Shangguan1, Xiaohong Yang1 and Ying Zha ng1
Abstract Objective: Vitamin D-dependent rickets type IA (VDDR-IA) is a rare autosomal recessive disorder characterized by the early onset of severe rickets. The objectives of this study were twofold: (1) to analyze the clinical characteristics and therapy of two patients with VDDR-IA from two separate Chinese families, and (2) investigate the CYP27B1 gene mutations in two large pedigrees. Methods: Medical history, clinical manifestations, physical examination, radiological findings and laboratory data were analyzed from two patients with VDDR-IA. Serum 1, 25-dihydroxyvitamin D [1, 25-(OH)2D3] of the two patients and their respective families were measured by ELISA and blood samples from both families was obtained for CYP27B1 gene sequence. Results: Two patients had typical manifestations and radiological evidence of rickets. Laboratory data showed hypocalcaemia and hypophosphataemia, along with high levels of serum alkaline phosphatase, parathyroid hormone and 25-hydroxyvitamin D3. However, serum 1,25-(OH)2D3 level were low in the patients but normal in their family members. Genetic sequence identified two patients were homozygous for a duplication mutation in exon 8 of CYP27B1 gene (c.1319_1325dupCCCACCC, p.Phe443Profs * 24). After treating with calcitriol and calcium, there was biochemical improvement with normalization of serum calcium and phosphorus, and radiographic evidence of compensatory skeletal mineralization. One patient developed nephrocalcinosis during follow-up. Conclusions: This study identified a recurrent seven-nucleotide insertion of CYP27B1 in two large pedigrees, and compared the clinical characteristics and individual therapy of two affected patients. Additionally, our experience further supports the notion that nephrocalcinosis can occur even on standard doses of calcitriol and oral calcium, and normal level of serum calcium, phosphorus, PTH and 25-(OH)D3. Keyword: Vitamin D-dependent rickets type IA, CYP27B1, Genetic sequence analysis, Treatment, Nephrocalcinosis
*Correspondence: [email protected] † Yunfei Li and Xin Yuan: Co-first author. 1 Department of Endocrinology, Genetics and Metabolism, Fuzhou Children’s Hospital of Fujian Medical University, No. 145, 817 Middle Road, Fuzhou 350005, China Full list of author information is available at the end of the article
Introduction Vitamin D consists of a group of biologically inactive, fat-soluble prohormones which exist in two major forms: ergocalciferol (vitamin D2) is mainly produced by plants and cholecalciferol (vitamin D3) is derived from 7-dehydrocholesterol in human skin by the action of UV sunlight rays in sunlight [1]. Both forms of vitamin D are activated by a two-step hydroxylation at carbons 25 and 1. The first step occurs in liver, with the
© The Author(s). 2020 Open Access Thi
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