Abstract

Fatal Familial Insomnia: Insight of the Most Common Genetic Prion Disease in China Based On the Analysis of 40 Patients

Author(s): Qi Shi, Kang Xiao, Wei Zhou, Jing Wang, Cao Chen, Chen Gao, Xiao-Ping Dong

Fatal familial insomnia (FFI) is one of the subtypes of human genetic prion diseases and is the most frequently identified genetic prion disease in China. In this study, the epidemiological, clinical, laboratory and genetic features of 40 Chinese FFI patients were systematically analyzed. Despite of the distribution in 12 provinces, apparently more cases located in Henan and Guangdong provinces. The median onset age was 51 year-old (from 19-70 y) and the gender ratio was 1:1.5 (M:F). 45% cases displayed clinical symptoms less than 50 y and 32.5% cases did not have definitely disease family history. Sleeping disturbances, mental problems and recognition disorders were most common foremost symptoms, in which sleeping disturbances and recognition disorders were significantly frequent in the patients with positive family history and those with the onset age ≥ 50 y, respectively. Sympathetic symptoms, such as excessive sweating, salivation and minor evening pyrexia, were commonly noticed. 85% patients showed hypertension and 57.5% had obvious weight loss. 37.9% cases were cerebrospinal fluid (CSF) 14-3-3 positive and 25% were CSF RT-QuIC positive. Sporadic Creutzfeldt-Jakob disease (sCJD) associated abnormalities on MRI were recorded only in 6 patients with the onset-age ≥ 50 y. 126 individual from 14 families conducted prion gene (PRNP) sequencing and 36 asymptomatic carriers of D178N mutation and M129M homozygous were identified, among them 7 mutation carriers from 5 families were in the parent-generation and 5 from 3 families were elder siblings of the probands. The median survival was 10 months varying from 5 to 30 months. This is the largest study on FFI patients in China, as well as in Asia, which is helpful to enrich the knowledge of FFI.