Wu Jing, Cao Qiaoyu, Lu Wei, Sun Chengjun, Li Qiuyue, Ye Rong, Cheng Ruoqian, Luo Feihong, Li Ming
Department of Pediatric Endocrinology and Inherited Metabolic Diseases, National Children's Medical Center, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China.
Department of Dermatology, National Children's Medical Center, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China.
Calcif Tissue Int. 2025 Apr 28;116(1):65. doi: 10.1007/s00223-025-01373-x.
Cutaneous-skeletal hypophosphatemia syndrome (CSHS) is a rare mosaic disorder that causes bone abnormalities due to hypophosphatemic rickets and skeletal dysplasia and is a significant health comorbidity. Conventional therapy involving multiple daily oral doses of phosphate and calcitriol for CSHS patients has limited effectiveness. We report the clinical features and therapeutic outcomes of the first Chinese child diagnosed with CSHS, who presented with bone fractures, a history of seizures, and recurrent gastrointestinal manifestations, including diarrhoea and bowel obstruction. The effectiveness of conventional therapy and an anti-FGF23 antibody (burosumab) was evaluated. Ultra-deep sequencing was performed on the patient's blood DNA, skin tissue, oral mucosa, and hair follicles to identify causative mutations. The child had a somatic mutation in the HRAS (p.G13R) gene, which was identified at low variant allele frequencies. We analysed the sequencing results from reported cases and determined that the sequencing of lesional tissues, such as skin and bone, is preferable to that of oral mucosa or potentially affected hair follicles for establishing a definitive diagnosis of CSHS. Compared with conventional phosphate therapy, burosumab resulted in a steady increase in blood phosphorus levels and significant improvements in patient mobility, pain outcomes and skeletal radiography. It is suggested that younger children may receive a higher initial dosage of burosumab for better outcomes. However, long-term follow-up is still necessary to confirm its efficacy and safety.
皮肤骨骼低磷血症综合征（CSHS）是一种罕见的嵌合性疾病，因低磷性佝偻病和骨骼发育异常导致骨骼畸形，是一种严重的健康合并症。针对CSHS患者的传统治疗方法是每日多次口服磷酸盐和骨化三醇，但其疗效有限。我们报告了首例被诊断为CSHS的中国儿童的临床特征和治疗结果，该患儿出现骨折、癫痫病史以及反复出现的胃肠道症状，包括腹泻和肠梗阻。评估了传统治疗方法和一种抗FGF23抗体（布罗索尤单抗）的疗效。对该患者的血液DNA、皮肤组织、口腔黏膜和毛囊进行了超深度测序，以确定致病突变。该患儿的HRAS（p.G13R）基因存在体细胞突变，其变异等位基因频率较低。我们分析了已报道病例的测序结果，确定对于明确诊断CSHS，对病变组织（如皮肤和骨骼）进行测序优于对口腔黏膜或可能受累的毛囊进行测序。与传统磷酸盐治疗相比，布罗索尤单抗使血磷水平稳步升高，患者的活动能力、疼痛状况和骨骼X线检查有显著改善。建议年龄较小的儿童可能需要更高的布罗索尤单抗初始剂量以获得更好的治疗效果。然而，仍需要长期随访以确认其疗效和安全性。
