青少年型Sandhoff病一例临床特点及基因分析

Clinical and molecular characteristics of a child with juvenile Sandhoff disease

目的 探讨青少年型Sandhoff病的临床及氨基己糖苷酶β-亚单位基因（HEXB）突变特点.方法 回顾性分析2012年5月广州市妇女儿童医疗中心内分泌代谢科确诊的1例青少年型Sandhoff病患儿的临床、头颅MRI及生化表现,采用荧光底物法分别测定外周血白细胞氨基己糖苷酶A（Hex A）及氨基己糖苷酶A和B（Hex A＆B）酶活性,PCR-DNA直接测序法进行HEXB突变分析.结果 患儿男,9岁,主因“走路不稳、讲话变慢并进行性加重3年”就诊,病情进展缓慢.头颅MRI表现为双侧小脑半球、小脑蚓脑沟明显加深,提示小脑萎缩.基底节区域波谱成像分析（MRS）提示左、右背部丘脑NAA/Cr、Cho/Cr、Cho/NAA比值均未见明显异常.白细胞Hex A活性为69.5nmol/（mg·h）[参考值150～ 360 nmol/（mg·h）],Hex A＆B活性为119 nmol/（mg·h）[参考值600～3 600 nmol/（mg·h）].HEXB基因突变分析显示c.1404delT（p.P468P fsX62）及c.1509-26G＞A复合杂合突变,前者为新缺失突变,后者为已知致病突变.随访18个月,病情缓慢进展.结论 青少年型Sandhoff病可表现为小脑性共济失调及小脑萎缩,酶学测定可见白细胞Hex A＆B活性明显降低,HEXB突变分析发现新突变c.1404delT（p.P468P fsX62）.

Objective To explore the clinical features and molecular mutation of HEXB gene in a case with juvenile Sandhoff disease.Method We retrospectively reviewed the clinical,neuroimaging and biochemical findings in this Chinese child with juvenile Sandhoff disease.Hexosaminidase A and hexosaminidase A ＆ B activities were measured in blood leukocytes by fluorometric assay.HEXB gene molecular analysis was performed by PCR and direct sequencing.Result The 9-year-old boy was admitted for psychomotor regression.He presented slowly progressive gait disorder and dysarthria during the last three years.Cranial MRI revealed a marked cerebellar atrophy with normal intensity in the thalamus and basal ganglia.Brain MRS showed normal in the thalamus and basal ganglia.Hexosaminidase A was 69.5 （mg·h） [normal controls 150-360 nmol/（mg · h）],hexosaminidase A ＆ B activity was 119 nmol/（mg · h） [normal controls 600-3 500 nmol/（mg · h）],confirming the diagnosis of Sandhoff disease.The patient was a compound heterozygote for a novel deletion mutation c.1404delT （p.P468P fsX62） and a reported mutation c.1509-26G ＞ A.Conclusion The clinical features of juvenile Sandhoff disease include ataxia,dysarthria and cerebellar atrophy.The enzyme assay and molecular analysis of HEXB gene can confirm the diagnosis of Sandhoff disease.The novel mutation c.1404delT（p.P468P fsX62） is a diseaserelated mutation.