Abstract：
Hajdu-Cheney syndrome (HCS) is an inherited skeletal disorder caused by mutations in the Notch homolog protein 2 gene (NOTCH2). Treatment of this rare disease is challenging because there are no established guidelines worldwide. Previous case reports using bisphosphonates, denosumab, or teriparatide suggested that curative treatment for HCS did not exist yet in terms of preventing the disease progression. Therefore, the efficacy of romosozumab for osteoporosis in patients with HCS needs to be evaluated. Herein, we report the case of a 43-year-old woman who had progressive acro-osteolysis and repeated fractures since the age of 29 years. Next-generation sequencing confirmed HCS with a mutation at nucleotide 6758G>A, leading to Trp2253Ter replacement in NOTCH2. Romosozumab treatment was initiated because she had already received bisphosphonate for more than 10 years at other hospitals. After 1 year of romosozumab treatment, the bone mineral density (BMD) increased by 10.2%, 6.3%, and 1.3%, with Z scores of -2.9, -1.6, and -1.2 at the lumbar spine, femoral neck, and total hip, respectively. In addition, C-telopeptide was suppressed by 26.4% (0.121 to 0.089 ng/mL), and procollagen type I N-terminal propeptide increased by 18.7% (25.2 to 29.9 ng/mL). This was the first report of romosozumab treatment in patient with osteoporosis and HCS in Korea. One year of romosozumab treatment provided substantial gains in BMD with maintaining the last acro-osteolytic status without deteriorating, representing a possible treatment option for HCS.
摘要：
Hajdu-Cheney综合征（HCS）是由Notch同源蛋白2基因（NOTCH2）突变引起的遗传性骨骼疾病。这种罕见疾病的治疗具有挑战性，因为全球范围内没有既定的指南。以前使用双膦酸盐的病例报告，denosumab,或特立帕肽提示,就预防疾病进展而言,尚不存在针对HCS的治愈性治疗.因此,需要评估romosozumab对HCS患者骨质疏松症的疗效.在这里，我们报道了一例43岁女性,该女性自29岁起出现进行性关节骨溶解和反复骨折.下一代测序证实HCS具有核苷酸6758G>A的突变，导致在NOTCH2中更换Trp2253Ter。Romosozumab开始治疗是因为她已经在其他医院接受双膦酸盐超过10年。romosozumab治疗1年后，骨密度(BMD)增加10.2%,6.3%,和1.3%，腰椎的Z评分为-2.9、-1.6和-1.2，股骨颈,和全髋关节，分别。此外,C端肽被抑制了26.4%（0.121至0.089ng/mL），和I型前胶原N端前肽增加了18.7％（25.2至29.9ng/mL）。这是romosozumab在韩国治疗骨质疏松症和HCS患者的第一份报告。一年的romosozumab治疗提供了BMD的实质性增加，并保持最后的无端溶骨状态而不恶化，代表HCS的可能治疗选择。
