中文摘要：

目的探讨致死性家族性失眠症（fatal familial insomnia，FFI）的临床和生物学特征。方法总结2例FFI患者的临床表现、治疗与转归特点，并追踪至死亡；对患者进行了较详细的生物学检查，包括生化、电生理、头颅MRI和PET—CT检查及朊蛋白（Prion Protein，PrP）基因测序。结果2例FFI患者的共性：阳性家族史，临床主要表现睡眠紊乱伴精神、行为异常；影像检查示全脑轻度萎缩（额叶略明显），对称性顶、额叶及丘脑葡萄糖代谢降低；PrP基因532位碱基G突变为A和129MM纯合子变异。例1病情进展相对缓慢，死亡时总病程3年余，以运动系统损害突出，脑脊液14—3—3蛋白阴性；例2的病情进展迅速，死亡时总病程仅半年，以内分泌功能障碍突出，脑脊液14—3—3蛋白阳性，PrP基因173位碱基T—C变异。结论2例FFI患者临床特点存在差异，可能与PrP基因突变及脑脊液14—3—3蛋白检测结果有关，有待进一步证实。

英文摘要：

Objective To explore the clinical and molecule features of two cases with fatal familial insomnia. Methods Routine clinical test, related ancillary test and genetic examination were conducted in two cases of fatal familial insomnia. Results Both cases had positive family history, clinical manifestations of sleep disorders associated with mental, behavioral abnormalities. Brain imaging showed mild cerebral atrophy （slightly obvious in the frontal lobe） and symmetry decrease of glucose metabolism in the top, frontal and thalamic regions. Both cases had PrP D178N/Met-129 mutation. Case one mainly presented with motor disorder and had a negative CSF 14-3-3. Case two mainly presented with endocrine symptoms and had a positive CSF 14-3-3. In terms of disease course, case one had a relatively slow disease course and died three years after onset while case two had a rapid disease course and died half year after onset. Conclusions The variable clinical features in two FFI cases may be explained by the positive CSF 14-3-3 protein and PrP gene mutation