常染色体显性遗传骨硬化症Ⅱ型的2例家系报道及文献复习

Two family reports and literature review of autosomal dominant osteopetrosis type Ⅱ

目的分析两例常染色体显性骨硬化症(autosomal dominant osteopetrosis,ADO)患者的临床特点,对先证者及其家系的致病基因突变进行研究。方法收集两例骨硬化症患者的的临床特征及实验室检查资料进行总结分析,并复习相关文献对该病的诊治思路进行归纳总结。结果基因检测显示先证者1的氯离子通道蛋白7(chloride channel protein 7,CLCN7)基因第24外显子新的错义突变,即p.Gly765Cys,先证者2的CLCN7的第10外显子发现了一个已知的错义突变,即p.Arg286Trp,两位先证者均有骨量异常增高表现,椎体呈“夹心饼”样改变,且两者均表现为血钙、磷和碱性磷酸酶水平正常,而乳酸脱氢酶和肌酸激酶水平升高。结论ADO患者主要表现为骨密度异常增高、骨脆性增加及容易骨折等,目前该疾病多采取对症治疗,严重时可导致贫血、血小板减少伴出血、频发感染、肝脾肿大等,通过文献复习进一步总结ADO的临床表现和诊疗特点。

Objective To analyze the clinical features of two patients with autosomal dominant osteopetrosis(ADO),and to explore the mutations in the causative genes in the probands and their family lines.Methods The clinical characteristics and laboratory examination data of the two ADO cases were collected and analyzed,and relevant literature was reviewed to summarize the diagnosis and treatment of the disease.Results Genetic testing revealed a new missense mutation in exon 24 of the chloride channel protein 7(CLCN7)gene,p.Gly765Cys,in proband 1,and a known missense mutation,p.Arg286Trp,in exon 10 of the CLCN7 gene in proband 2.Both probands manifested abnormally high bone mass and"sandwich"vertebral body changes,but both had normal blood calcium,phosphorus and alkaline phosphatase levels and elevated lactate dehydrogenase and creatine kinase levels.Conclusion Patients with ADO mainly exhibit abnormally high bone density,increased bone fragility and susceptibility to fracture.Currently,the disease is mostly treated symptomatically.In severe cases,anemia,thrombocytopenia with hemorrhage,frequent infections,and liver and spleen enlargement may occur.Further literature review will better summarize the clinical presentation,diagnosis and therapeutic features of ADO.