Phenotypes and Genotypes of Children with Vitamin D-Dependent Rickets Type 1A: A Single Tertiary Pediatric Center in Vietnam
<b>Background</b>: Vitamin D-dependent rickets type 1A (VDDR1A) is a rare autosomal recessive disorder caused by mutations in the <i>CYP27B1</i> gene, leading to a deficiency in active vitamin D (1,25-dihydroxyvitamin D). This study examines the genotypic and phenotypic chara...
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MDPI AG
2025-04-01
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| author | Thi Anh Thuong Tran Tran Minh Dien Ngoc Lan Nguyen Khanh Ngoc Nguyen Thi Bich Ngoc Can Bui Phuong Thao Nguyen Thi Thuy Hong Van Khanh Tran Thinh Huy Tran Ngo Xuan Khoa Nguyen Thi Kim Lien Nguyen Thien Tao Huy Hoang Nguyen Chi Dung Vu |
| author_facet | Thi Anh Thuong Tran Tran Minh Dien Ngoc Lan Nguyen Khanh Ngoc Nguyen Thi Bich Ngoc Can Bui Phuong Thao Nguyen Thi Thuy Hong Van Khanh Tran Thinh Huy Tran Ngo Xuan Khoa Nguyen Thi Kim Lien Nguyen Thien Tao Huy Hoang Nguyen Chi Dung Vu |
| author_sort | Thi Anh Thuong Tran |
| collection | DOAJ |
| description | <b>Background</b>: Vitamin D-dependent rickets type 1A (VDDR1A) is a rare autosomal recessive disorder caused by mutations in the <i>CYP27B1</i> gene, leading to a deficiency in active vitamin D (1,25-dihydroxyvitamin D). This study examines the genotypic and phenotypic characteristics of VDDR1A in Vietnamese children. <b>Patients and Methods</b>: A retrospective analysis was conducted on 19 Vietnamese children diagnosed with VDDR1A. Clinical, radiological, biochemical, and molecular data were collected. Rickets Severity Scores (RSSs), biochemical parameters, and height standard deviation scores (HtSDSs) were used to assess the severity of the condition. <b>Results:</b> The study included 19 children from 17 families (ten males and nine females). The median age of rickets diagnosis was 19.2 months, while with VDDR1A, the median time of diagnosis was 7.5 months. Common symptoms among the children included thickened wrists and ankles (19/19), genu varum or genu valgum (18/19), failure to thrive (18/19), rachitic rosary (12/19), and delayed walking (11/19). The radiographic features showed that all children had cupping, splaying, and fraying, twelve children had rachitic rosary, and six exhibited pseudofractures. The biochemical findings showed severe hypocalcemia, normal or mildly low serum phosphate, elevated alkaline phosphatase and parathyroid hormone levels, and normal serum 25-hydroxyvitamin D levels. Genetic analysis identified biallelic <i>CYP27B1</i> variants, including one known pathogenic frameshift mutation, c.1319_1325dup p.(Phe443Profs*24), one novel likely pathogenic missense variant, c.616C>T p.(Arg206Cys), and one novel pathogenic frameshift mutation, c.96_97del p.(Ala33Thrfs*299). The c.1319_1325dup p.(Phe443Profs*24) variant was the most common, present in 18 out of 19 children. <b>Conclusions:</b> The children with VDDR1A in this study presented with growth failure and skeletal deformities. Key findings included severe hypocalcemia, elevated alkaline phosphatase and parathyroid hormone levels, normal or elevated 25(OH)D, and high RSSs. Predominant frameshift mutations in <i>CYP27B1</i>, especially c.1319_1325dup, highlighted the importance of early genetic diagnosis for optimal management. Additionally, two novel <i>CYP27B1</i> variants were identified, expanding the known mutation spectrum of VDDR1A. |
| format | Article |
| id | doaj-art-58e297bc869d4766b0613ff6dc7917b3 |
| institution | OA Journals |
| issn | 2075-4418 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
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| series | Diagnostics |
| spelling | doaj-art-58e297bc869d4766b0613ff6dc7917b32025-08-20T02:15:55ZengMDPI AGDiagnostics2075-44182025-04-0115791810.3390/diagnostics15070918Phenotypes and Genotypes of Children with Vitamin D-Dependent Rickets Type 1A: A Single Tertiary Pediatric Center in VietnamThi Anh Thuong Tran0Tran Minh Dien1Ngoc Lan Nguyen2Khanh Ngoc Nguyen3Thi Bich Ngoc Can4Bui Phuong Thao5Nguyen Thi Thuy Hong6Van Khanh Tran7Thinh Huy Tran8Ngo Xuan Khoa9Nguyen Thi Kim Lien10Nguyen Thien Tao11Huy Hoang Nguyen12Chi Dung Vu13Department of Paediatrics, Hanoi Medical University, Hanoi 11521, VietnamVietnam National Children’s Hospital, Hanoi 11512, VietnamCenter for Gene and Protein Research, Hanoi Medical University, Hanoi 11521, VietnamDepartment of Paediatrics, Hanoi Medical University, Hanoi 11521, VietnamCenter of Endocrinology, Metabolism, Genetic/Genomics and Molecular Therapy, Vietnam National Children’s Hospital, Hanoi 11512, VietnamCenter of Endocrinology, Metabolism, Genetic/Genomics and Molecular Therapy, Vietnam National Children’s Hospital, Hanoi 11512, VietnamDepartment of Paediatrics, Hanoi Medical University, Hanoi 11521, VietnamCenter for Gene and Protein Research, Hanoi Medical University, Hanoi 11521, VietnamCenter for Gene and Protein Research, Hanoi Medical University, Hanoi 11521, VietnamCenter for Gene and Protein Research, Hanoi Medical University, Hanoi 11521, VietnamInstitute of Genome Research, Vietnam Academy of Science and Technology, Hanoi 100000, VietnamInstitute of Genome Research, Vietnam Academy of Science and Technology, Hanoi 100000, VietnamInstitute of Genome Research, Vietnam Academy of Science and Technology, Hanoi 100000, VietnamDepartment of Paediatrics, Hanoi Medical University, Hanoi 11521, Vietnam<b>Background</b>: Vitamin D-dependent rickets type 1A (VDDR1A) is a rare autosomal recessive disorder caused by mutations in the <i>CYP27B1</i> gene, leading to a deficiency in active vitamin D (1,25-dihydroxyvitamin D). This study examines the genotypic and phenotypic characteristics of VDDR1A in Vietnamese children. <b>Patients and Methods</b>: A retrospective analysis was conducted on 19 Vietnamese children diagnosed with VDDR1A. Clinical, radiological, biochemical, and molecular data were collected. Rickets Severity Scores (RSSs), biochemical parameters, and height standard deviation scores (HtSDSs) were used to assess the severity of the condition. <b>Results:</b> The study included 19 children from 17 families (ten males and nine females). The median age of rickets diagnosis was 19.2 months, while with VDDR1A, the median time of diagnosis was 7.5 months. Common symptoms among the children included thickened wrists and ankles (19/19), genu varum or genu valgum (18/19), failure to thrive (18/19), rachitic rosary (12/19), and delayed walking (11/19). The radiographic features showed that all children had cupping, splaying, and fraying, twelve children had rachitic rosary, and six exhibited pseudofractures. The biochemical findings showed severe hypocalcemia, normal or mildly low serum phosphate, elevated alkaline phosphatase and parathyroid hormone levels, and normal serum 25-hydroxyvitamin D levels. Genetic analysis identified biallelic <i>CYP27B1</i> variants, including one known pathogenic frameshift mutation, c.1319_1325dup p.(Phe443Profs*24), one novel likely pathogenic missense variant, c.616C>T p.(Arg206Cys), and one novel pathogenic frameshift mutation, c.96_97del p.(Ala33Thrfs*299). The c.1319_1325dup p.(Phe443Profs*24) variant was the most common, present in 18 out of 19 children. <b>Conclusions:</b> The children with VDDR1A in this study presented with growth failure and skeletal deformities. Key findings included severe hypocalcemia, elevated alkaline phosphatase and parathyroid hormone levels, normal or elevated 25(OH)D, and high RSSs. Predominant frameshift mutations in <i>CYP27B1</i>, especially c.1319_1325dup, highlighted the importance of early genetic diagnosis for optimal management. Additionally, two novel <i>CYP27B1</i> variants were identified, expanding the known mutation spectrum of VDDR1A.https://www.mdpi.com/2075-4418/15/7/918vitamin D-dependent rickets type 1A<i>CYP27B1</i>Vietnamese childrenskeletal deformitiesrickethypocalcemia |
| spellingShingle | Thi Anh Thuong Tran Tran Minh Dien Ngoc Lan Nguyen Khanh Ngoc Nguyen Thi Bich Ngoc Can Bui Phuong Thao Nguyen Thi Thuy Hong Van Khanh Tran Thinh Huy Tran Ngo Xuan Khoa Nguyen Thi Kim Lien Nguyen Thien Tao Huy Hoang Nguyen Chi Dung Vu Phenotypes and Genotypes of Children with Vitamin D-Dependent Rickets Type 1A: A Single Tertiary Pediatric Center in Vietnam Diagnostics vitamin D-dependent rickets type 1A <i>CYP27B1</i> Vietnamese children skeletal deformities ricket hypocalcemia |
| title | Phenotypes and Genotypes of Children with Vitamin D-Dependent Rickets Type 1A: A Single Tertiary Pediatric Center in Vietnam |
| title_full | Phenotypes and Genotypes of Children with Vitamin D-Dependent Rickets Type 1A: A Single Tertiary Pediatric Center in Vietnam |
| title_fullStr | Phenotypes and Genotypes of Children with Vitamin D-Dependent Rickets Type 1A: A Single Tertiary Pediatric Center in Vietnam |
| title_full_unstemmed | Phenotypes and Genotypes of Children with Vitamin D-Dependent Rickets Type 1A: A Single Tertiary Pediatric Center in Vietnam |
| title_short | Phenotypes and Genotypes of Children with Vitamin D-Dependent Rickets Type 1A: A Single Tertiary Pediatric Center in Vietnam |
| title_sort | phenotypes and genotypes of children with vitamin d dependent rickets type 1a a single tertiary pediatric center in vietnam |
| topic | vitamin D-dependent rickets type 1A <i>CYP27B1</i> Vietnamese children skeletal deformities ricket hypocalcemia |
| url | https://www.mdpi.com/2075-4418/15/7/918 |
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