Clinical and genetic analysis of two Chinese families with vitamin D-dependent rickets type IA and follow-up
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 separat...
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| Format: | Article |
| Language: | English |
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BMC
2020-10-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13023-020-01558-7 |
| _version_ | 1818323122015698944 |
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| author | Yunfei Li Xin Yuan Ruimin Chen Xiangquan Lin Huakun Shangguan Xiaohong Yang Ying Zhang |
| author_facet | Yunfei Li Xin Yuan Ruimin Chen Xiangquan Lin Huakun Shangguan Xiaohong Yang Ying Zhang |
| author_sort | Yunfei Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T11:07:40Z |
| format | Article |
| id | doaj.art-af4417c86f554662b5d9839a867b1fdc |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-13T11:07:40Z |
| publishDate | 2020-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-af4417c86f554662b5d9839a867b1fdc2022-12-21T23:48:56ZengBMCOrphanet Journal of Rare Diseases1750-11722020-10-011511910.1186/s13023-020-01558-7Clinical and genetic analysis of two Chinese families with vitamin D-dependent rickets type IA and follow-upYunfei Li0Xin Yuan1Ruimin Chen2Xiangquan Lin3Huakun Shangguan4Xiaohong Yang5Ying Zhang6Department of Endocrinology, Genetics and Metabolism, Fuzhou Children’s Hospital of Fujian Medical UniversityDepartment of Endocrinology, Genetics and Metabolism, Fuzhou Children’s Hospital of Fujian Medical UniversityDepartment of Endocrinology, Genetics and Metabolism, Fuzhou Children’s Hospital of Fujian Medical UniversityDepartment of Endocrinology, Genetics and Metabolism, Fuzhou Children’s Hospital of Fujian Medical UniversityDepartment of Endocrinology, Genetics and Metabolism, Fuzhou Children’s Hospital of Fujian Medical UniversityDepartment of Endocrinology, Genetics and Metabolism, Fuzhou Children’s Hospital of Fujian Medical UniversityDepartment of Endocrinology, Genetics and Metabolism, Fuzhou Children’s Hospital of Fujian Medical UniversityAbstract 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.http://link.springer.com/article/10.1186/s13023-020-01558-7Vitamin D-dependent rickets type IACYP27B1Genetic sequence analysisTreatmentNephrocalcinosis |
| spellingShingle | Yunfei Li Xin Yuan Ruimin Chen Xiangquan Lin Huakun Shangguan Xiaohong Yang Ying Zhang Clinical and genetic analysis of two Chinese families with vitamin D-dependent rickets type IA and follow-up Orphanet Journal of Rare Diseases Vitamin D-dependent rickets type IA CYP27B1 Genetic sequence analysis Treatment Nephrocalcinosis |
| title | Clinical and genetic analysis of two Chinese families with vitamin D-dependent rickets type IA and follow-up |
| title_full | Clinical and genetic analysis of two Chinese families with vitamin D-dependent rickets type IA and follow-up |
| title_fullStr | Clinical and genetic analysis of two Chinese families with vitamin D-dependent rickets type IA and follow-up |
| title_full_unstemmed | Clinical and genetic analysis of two Chinese families with vitamin D-dependent rickets type IA and follow-up |
| title_short | Clinical and genetic analysis of two Chinese families with vitamin D-dependent rickets type IA and follow-up |
| title_sort | clinical and genetic analysis of two chinese families with vitamin d dependent rickets type ia and follow up |
| topic | Vitamin D-dependent rickets type IA CYP27B1 Genetic sequence analysis Treatment Nephrocalcinosis |
| url | http://link.springer.com/article/10.1186/s13023-020-01558-7 |
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