摘要
目的对2006年以来克雅病监测网络监测到的10例家族型致死性失眠症(fatal familial insomnia,FFI)确诊病例进行临床特征分析。方法应用世界卫生组织(WHO)推荐的《克雅病诊断标准》对报告病例进行诊断,对其主要临床症状、家族史及病理特征进行分析。结果 FFI主要临床症状为失眠、自主神经功能异常及肌阵挛。自2006年克雅病监测网络开始监测,迄今已确诊10例家族型致死性失眠症患者。患者平均发病年龄38岁(19～55岁),首发症状多种多样,包括睡眠节律的改变、视觉改变、头晕以及厌食。睡眠节律的改变出现在所有的病例中并且持续整个病程。患者也出现交感神经兴奋、记忆力丧失、运动障碍、肌阵挛及高血压症状。平均病程9.5个月。脑电图及磁共振成像(MRI)没有显示特殊的异常,脑脊液14-3-3蛋白在8个检测病例中有5例阳性。8例病例出现与疾病相关的家族史。病理检测发现丘脑部位出现明显的神经元损伤。结论中国的FFI病例与高加索人具有相似的临床特征,与其他遗传型克雅病比较,D178N突变的FFI病例在中国具有相对较高的出现频率。
Objective To study the clinical and familial features of the fatal familial insomnia（FFI）,an autosomal dominant prion disease clinically characterized by inattention,sleep loss,dysautonomia,and motor signs.MethodsFFI cases were identified and diagnosed based on the WHO recommended criteria for Creutzfeldt-Jakob disease（CJD）,and their clinical features and familial characteristics were analyzed.Blood samples were obtained from available family members of cases and the mutation of D178N in the prion protein gene（PRNP）was detected by polymerase chain reaction（PCR）.ResultsA total of 10 FFI cases were identified and diagnosed by the WHO criteria from the surveillance network for CJD in China since 2006.The onsets were from ages 19 to 55 with the median at 38 years old.The foremost symptoms seem to be various,including sleep disturbances,vision disorder,dizziness and anorexia.Sleep disturbances appeared in all cases and lasted during their full clinical courses.Progressive sympathetic symptoms,memory loss,movement disturbances,myoclonus and hypertension were also frequently observed.The median duration of the 10 FFI cases was 9.5 months.There were no special abnormalities detected by Electroencephalographic（EEG）and magnetic resonance imaging（MRI）.14-3-3 protein in cerebrospinal fluid（CSF） was positive in five out of eight tested patients.Clear family diseaseassociated histories were found in 8 patients and clear severe neuronal damage was detected in the thalamus region of 3 FFI cases.Blood samples from available family members of 4 cases were obtained;no mutations were found among the 14 family members of case 3 while one of his cousins died of a kind of unknown neurological disease;the mothers of cases 5 and 6 carried D178N mutation in PRNP gene but clinically were normal and healthy while no D178N mutation was found in other available family members from these two cases;one of his brother and this brother′s son were detected D178N mutation from the case 7 but not in the other 9 family members.ConclusionsFFI cases in China share similar clinical characteristics as that of Caucasian patients.Comparing to other genetic CJD associated mutations,the mutation of D178N in PRNP gene is frequently detected in FFI cases identified in China.
出处
《中国病毒病杂志》
CAS
2012年第3期197-201,共5页
Chinese Journal of Viral Diseases
基金
传染病预防控制国家重点实验室基金(2008SKLID102
2011SKLID211)
