新生儿恶性常染色体隐性遗传骨硬化症一例报道

One case report of neonatal malignant autosomal recessive osteopetrosis

目的:通过1例以血小板减少、骨密度增高为主要表现的恶性常染色体隐性遗传骨硬化症(ARO)患儿的病例报告,以期加强对ARO临床表现及基因型特点的认识,从而提高该病诊治水平。方法:结合1例新生儿恶性ARO患儿临床诊治过程及相关文献报道,对该病病因、临床表现、基因型特点及诊治进行讨论。结果:22日龄男婴因发热2 d、发现皮肤出血点1 d为主诉入院,查体颜面部可见散在出血点,按压不褪色,查血小板23×10^(9 )L^(-1),X线胸片示肋骨骨质密度增高,CLCN7基因检测发现存在chr16:1506200 c.824_830delTCTTCGA移码突变复合杂合7-17号外显子重复突变,该类型基因突变国内外尚未见报道。患儿移码突变源于其父亲,CNV重复突变遗传自其母亲,且其父母均未发病,根据基因型及患儿表型确诊为ARO。经对症及支持等治疗后患儿病情好转,但出院后未至门诊复查,1个月后死亡。结论:对于新生儿不明原因的发热、血小板减少,除外常见原因,需警惕罕见病因,如新生儿恶性ARO,应积极完善相关基因检测,以免漏诊误诊、延误治疗。

Objective:To enhance the understanding of the clinical manifestations and genotype characteristics of osteosclerosis,and to support the diagnosis and treatment of the disease by analyzing a newborn autosomal recessive osteopetrosis(ARO)patient with thrombocytopenia and increased bone density.Methods:Recessively analyzed the etiology,clinical manifestations,genotypes,diagnosis and treatment of the case with neonatal malignant ARO and discussed the characteristics of the disease by literature review.Results:A 22-day-old boy was admitted into the hospital due to fever for two days and the observation of face bleeding points.Scattered indelible bleeding point can be identified throughout the body.Significant low level of blood platelet and increased bone density in ribs were found as well.A novel parental heterozygous mutation c.824_830delTCTTCGA of CLCN gene was identified in this patient,and a maternal gain of CNV was also detected covering the exon 717 of the gene.This patient was diagnosed ARO.The baby was getting better after symptomatic treatments and later discharged.However,he failed to follow up in the clinic,and died in a month.Conclusion:As a neonatal malignant disease,pediatric doctors should consider ARO in mind when encounter unexplained fever and thrombocytopenia in neonates,and actively improve the relevant genetic testing to avoid misdiagnosis and delay treatment.