Wang Jing, Xiao Kang, Zhou Wei, Shi Qi, Dong Xiao Ping
State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Center of Global Public Health, Chinese Center for Disease Control and Prevention, Beijing, China.
J Clin Neurol. 2019 Apr;15(2):184-190. doi: 10.3988/jcn.2019.15.2.184. Epub 2019 Mar 11.
Gerstmann-Sträussler-Scheinker disease (GSS) with a proline-to-leucine mutation at codon 102 (P102L) in the gene is the most frequently reported GSS subtype worldwide. This study aimed to determine the epidemiological, clinical, genetic, and laboratory characteristics of 12 Chinese patients with P102L-associated GSS (henceforth P102L GSS).
The enrolled P102L GSS cases were analyzed according to the diagnostic criteria for Creutzfeldt-Jakob disease (CJD) issued by the China National Health Commission.
The median onset age was 50 years (range 34 to 67 years) and sex ratio was 1:2 (males:females). Most patients displayed more than one foremost symptom. Movement symptoms were frequently reported (9 of the 12 cases), followed by rapidly progressing dementia (7 cases), mental problems (5 cases), and slowly progressing dementia (2 cases). Almost all cases displayed more sporadic CJD (sCJD)-associated neurological symptoms and signs as time progressed. Five (45.5%) of 11 cases were cerebrospinal fluid 14-3-3 positive, and 2 (25%) of 8 cases exhibited periodic sharp wave complexes in electroencephalograms. MRI abnormalities were detected in all 11 of the scanned patients. Methionine homozygous genotype at codon 129 (M129M) and glutamic acid homozygous at codon 219 (E219E) homozygosity was present in 11 cases, while 1 case was M129M homozygous and glutamic acid/lysine heterozygous at codon 219 (E219K) heterozygous. Ten of the 12 cases recalled a disease-related family history during the clinical interviews. The median survival from symptom onset of the seven dead cases was 16 months (range 10 to 44 months). Patients showing the sCJD phenotype (rapidly progressing dementia) appeared to be associated with a shorter survival time.
The indistinguishable clinical features of P102L GSS patients with sCJD, especially in the early stage, support the importance of testing for diagnosing GSS.
在基因密码子102处发生脯氨酸到亮氨酸突变（P102L）的格斯特曼-施特劳斯勒-谢inker病（GSS）是全球报道最频繁的GSS亚型。本研究旨在确定12例中国P102L相关GSS患者（以下简称P102L GSS）的流行病学、临床、遗传和实验室特征。
根据中国国家卫生健康委员会发布的克雅氏病（CJD）诊断标准，对纳入的P102L GSS病例进行分析。
发病年龄中位数为50岁（范围34至67岁），性别比为1:2（男性:女性）。大多数患者表现出不止一种主要症状。运动症状经常被报道（12例中的9例），其次是快速进展性痴呆（7例）、精神问题（5例）和缓慢进展性痴呆（2例）。随着时间的推移，几乎所有病例都表现出更多与散发性CJD（sCJD）相关的神经症状和体征。11例中的5例（45.5%）脑脊液14-3-3呈阳性，8例中的2例（25%）脑电图显示周期性锐波复合波。11例接受扫描的患者均检测到MRI异常。11例患者在密码子129处为甲硫氨酸纯合基因型（M129M），在密码子219处为谷氨酸纯合（E219E）纯合子，而1例为M129M纯合子且在密码子219处为谷氨酸/赖氨酸杂合（E219K）杂合子。12例患者中有10例在临床访谈中回忆起与疾病相关的家族史。7例死亡病例从症状出现到死亡的中位生存期为16个月（范围10至44个月）。表现出sCJD表型（快速进展性痴呆）的患者似乎生存期较短。
P102L GSS患者与sCJD难以区分的临床特征，尤其是在早期阶段特点，支持了检测对于诊断GSS的重要性。
