未经证实:维生素D依赖性1A型病(VDDR1A)是一种由CYP27B1基因缺乏引起的罕见常染色体隐性遗传疾病。本研究旨在调查中国南方地区VDDR1A儿童的表型和基因型特征,并评估其长期治疗效果。
UNASSIGNED:12名来自中国南方的VDDR1A儿童被纳入本研究。他们的临床,放射学,生物化学,和分子研究结果进行回顾性分析。病严重程度评分(RSS),生化参数,和身高标准差评分(HtSDS)用于评估临床结果。
未经授权:该VDDR1A队列中包括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是行走延迟(10/12)和严重的生长迟缓(9/12)。诊断时的HtSDS与年龄呈负相关(p<0.05)。所有患者均出现低钙血症,低磷酸盐血症,血清碱性磷酸酶和甲状旁腺激素升高,和高RSS在诊断。在所有患者中发现了CYP27B1基因的两个等位基因变体,包括九种不同的变体,四个已知和五个小说,与c.1319_1325dupCCCACCC(p。Phe443Profs*24)是最常见的。所有患者确诊后均给予骨化三醇和钙剂治疗,所有患者均随访6个月至15.6年。HTSDS,RSS,在治疗的最初几年中,发现生化指标有所改善。然而,只有5名患者有良好的依从性.尽管RSS和生化指标显著提高,从诊断到最后一次就诊,HtSDS变化不显著,7例患者身材矮小(HtSDS<-2)。
UNASSIGNED:我们的研究扩展了VDDR1A的突变谱,并在中国南方发现了CYP27B1基因的热点变体。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患者身高改善的挑战。
UNASSIGNED: Vitamin D-dependent rickets type 1A (VDDR1A) is a rare autosomal recessive disorder caused by deficiency of the CYP27B1 gene. This
study aims to investigate the phenotypic and genotypic features of VDDR1A children in southern China and evaluate the long-term therapeutic effects.
UNASSIGNED: 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.
UNASSIGNED: 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 (p < 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 CYP27B1 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).
UNASSIGNED: Our
study extends the mutational spectrum of VDDR1A and finds a hotspot variant of the CYP27B1 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.