Lin Yunting, Guan Zhihong, Mei Huifen, Zhang Wen, Zhou Zhizi, Su Ling, Cheng Jing, Zheng Ruidan, Liang Cuili, Cai Yanna, Yin Xi, Wu Dongyan, Liu Li, Zeng Chunhua
Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, China.
Front Pediatr. 2022 Nov 4;10:1007219. doi: 10.3389/fped.2022.1007219. eCollection 2022.
Vitamin D-dependent rickets type 1A (VDDR1A) is a rare autosomal recessive disorder caused by deficiency of the gene. This study aims to investigate the phenotypic and genotypic features of VDDR1A children in southern China and evaluate the long-term therapeutic effects.
Twelve children from southern China with VDDR1A were enrolled in this study. Their clinical, radiological, biochemical, and molecular findings were analyzed retrospectively. The rickets severity score (RSS), biochemical parameters, and height standard deviation score (HtSDS) were used to evaluate clinical outcomes.
Six males and six females were included in this VDDR1A cohort. The age of onset was from 6 months to 1.8 years, and the age at diagnosis was 2.1 ± 0.8 years. The most common clinical symptoms at diagnosis were delayed walking (10/12) and severe growth retardation (9/12). HtSDS at diagnosis was negatively associated with age (< 0.05). All patients presented with hypocalcemia, hypophosphatemia, increased serum alkaline phosphatase and parathyroid hormone, and high RSS at diagnosis. Two allelic variants of the gene were identified in all patients, including nine different variants, four known and five novel, with c.1319_1325dupCCCACCC(p.Phe443Profs*24) being the most frequent. All patients were treated with calcitriol and calcium after diagnosis, and all patients but one were followed-up from 6 months to 15.6 years. HtSDS, RSS, and biochemical parameters were found to be improved during the first few years of the treatment. However, only five patients had good compliance. Although RSS and biochemical parameters were significantly improved, the HtSDS change was not significant from the time of diagnosis to the last visit, and seven patients remained of a short stature (HtSDS < -2).
Our study extends the mutational spectrum of VDDR1A and finds a hotspot variant of the gene in southern China. The results reconfirm the importance of early diagnosis and treatment compliance and reveal the challenge of height improvement in VDDR1A patients.
1A型维生素D依赖性佝偻病（VDDR1A）是一种由基因缺陷引起的罕见常染色体隐性疾病。本研究旨在调查中国南方VDDR1A患儿的表型和基因型特征，并评估长期治疗效果。
本研究纳入了12名来自中国南方的VDDR1A患儿。对他们的临床、放射学、生化和分子学检查结果进行回顾性分析。采用佝偻病严重程度评分（RSS）、生化参数和身高标准差评分（HtSDS）来评估临床结局。
该VDDR1A队列包括6名男性和6名女性。发病年龄为6个月至1.8岁，诊断年龄为2.1±0.8岁。诊断时最常见的临床症状为行走延迟（10/12）和严重生长发育迟缓（9/12）。诊断时的HtSDS与年龄呈负相关（<0.05）。所有患者诊断时均出现低钙血症、低磷血症、血清碱性磷酸酶和甲状旁腺激素升高以及高RSS。在所有患者中鉴定出该基因的两个等位基因突变，包括9种不同的突变，其中4种已知，5种为新发现的突变，c.1319_1325dupCCCACCC（p.Phe443Profs*24）最为常见。所有患者诊断后均接受骨化三醇和钙剂治疗，除1例患者外，所有患者均随访6个月至15.6年。在治疗的最初几年中，发现HtSDS、RSS和生化参数有所改善。然而，只有5例患者依从性良好。虽然RSS和生化参数有显著改善，但从诊断到最后一次随访，HtSDS变化不显著，7例患者仍身材矮小（HtSDS<-2）。
我们的研究扩展了VDDR1A的突变谱，并在中国南方发现了该基因的一个热点突变。结果再次证实了早期诊断和治疗依从性的重要性，并揭示了VDDR1A患者身高改善面临的挑战。
