皮肤骨骼低磷综合征2例患者临床研究并文献复习

The clinical investigation of two cases of cutaneous skeletal hypophosphatemia syndrome and review of literature

目的:观察2例散发的皮肤骨骼低磷综合征(cutaneous skeletal hypophosphatemia syndrome,CSHS)患者的临床特征及影像学表现,并进行致病基因突变检测和药物治疗干预,同时复习相关文献进行综合分析。方法:收集2例CSHS患者的详细病史以及体格检查、血液生化检测和影像学检查等结果,并采集患者的外周血和皮损处皮肤组织样本,分别抽提DNA进行KRAS、NRAS、HRAS基因Sanger测序。结果:2例CSHS患者均表现为全身疼痛伴进行性加重的活动障碍,脊柱侧弯、多处骨折,并伴有腰臀部黑素痣;血生化检测显示,其血磷水平降低,分别为0.44 mmol/L和0.46 mmol/L,碱性磷酸酶(alkaline phosphatase,ALP)升高(157 U/L和277 U/L),成纤维生长因子23(fibroblast growth factor 23,FGF-23)水平增高(57.0 ng/L和118.5 ng/L);骨密度检测结果提示,骨密度显著降低。给予患者中性磷溶液和骨化三醇治疗后,其临床症状明显改善。2例患者的外周血及皮损处皮肤组织DNA中均未检测到已知基因突变。结论:CSHS是临床罕见的代谢性骨病,其发病机制目前尚不明确,诊断主要依靠临床表现、生化检测、特征性骨软化影像学表现,基因检测出RAS突变即可确诊。

Objective:To explore the clinical features,imaging manifestations,gene mutations and treatment response of 2 sporadic cases of cutaneous skeletal hypophosphatemia syndrome.Methods:The case history,clinical presentation and laboratory and imaging data were reviewed.The genomic DNA was extracted from peripheral blood and skin tissue of patients were sequenced by Sanger sequencing for detection of KRAS、NRAS and HRAS gene mutations.Results:Both patients had bone pain accompanied with progressive difficulty in movement,scoliosis,multiple fractures,and melanocytic nevi located in waist and hips.The laboratory investigation revealed decreased blood phosphorus level(0.44 mmol/L and 0.46 mmol/L)and elevated levels of alkaline phosphatase(ALP)(157 U/L and 277 U/L)and fibroblast growth factor 23(FGF-23)(57.0 ng/L and 118.5 ng/L).The dual-energy X-ray absorption detector indicated a significant decrease in bone density.The symptoms were significantly improved after treatment with neutral phosphorus and vitamin D.No related gene mutation was identified.Conclusions:Cutaneous skeletal hypophosphatemia syndrome is a rare metabolic bone disease with unclear pathogenesis.Currently,the diagnosis still relies on characteristic clinical,laboratory and imaging manifestation.Identification of RAS gene mutations will help the establishment of the diagnosis.