Creutzfeldt-Jakob disease presenting as Korsakoff syndrome caused by E196A mutation in PRNP gene:A case report

BACKGROUND Prion diseases are a group of degenerative nerve diseases that are caused by infectious prion proteins or gene mutations.In humans,prion diseases result from mutations in the prion protein gene(PRNP).Only a limited number of cases involving a specific PRNP mutation at codon 196(E196A)have been reported.The coexistence of Korsakoff syndrome in patients with Creutzfeldt-Jakob disease(CJD)caused by E196A mutation has not been documented in the existing literature.CASE SUMMARY A 61-year-old Chinese man initially presented with Korsakoff syndrome,followed by rapid-onset dementia,visual hallucinations,akinetic mutism,myoclonus,and hyperthermia.The patient had no significant personal or familial medical history.Magnetic resonance imaging of the brain revealed extensive hyperintense signals in the cortex,while positron emission tomography/computed tomography showed a diffuse reduction in cerebral cortex metabolism.Routine biochemical and microorganism testing of the cerebrospinal fluid(CSF)yielded normal results.Tests for thyroid function,human immunodeficiency virus,syphilis,vitamin B1 and B12 levels,and autoimmune rheumatic disorders were normal.Blood and CSF tests for autoimmune encephalitis and autoantibody-associated paraneoplastic syndrome yielded negative results.A test for 14-3-3 protein in the CSF yielded negative results.Whole-genome sequencing revealed a diseasecausing mutation in PRNP.The patient succumbed to the illness 11 months after the initial symptom onset.CONCLUSION Korsakoff syndrome,typically associated with alcohol intoxication,also manifests in CJD patients.Individuals with CJD along with PRNP E196A mutation may present with Korsakoff syndrome.

克-雅病合并神经系统副肿瘤综合征一例

患者男性,58岁。因记忆力减退15天余,于2021年5月13日首次入院。患者入院前15天无明显诱因出现记忆力减退,表现为忘记关车门、服药,烹饪能力下降,买菜、打麻将时计算力下降,伴夜间双下肢及背部肌肉疼痛,无头痛、恶心、呕吐,无饮水呛咳,无视物旋转,至我院门诊就诊,门诊以“痴呆”收入院。患者自发病以来,精神、睡眠、饮食欠佳,大小便正常,体重无明显变化。

Genetic Prion Disease:Insight from the Features and Experience of China National Surveillance for Creutzfeldt-Jakob Disease

Human genetic prion diseases(gPrDs)are directly associated with mutations and insertions in the PRNP(Prion Protein)gene.We collected and analyzed the data of 218 Chinese gPrD patients identified between Jan 2006 and June 2020.Nineteen different subtypes were identified and gPrDs accounted for 10.9%of all diagnosed PrDs within the same period.Some subtypes of gPrDs showed a degree of geographic association.The age at onset of Chinese gPrDs peaked in the 50–59 year group.Gerstmann–Sträussler–Scheinker syndrome(GSS)and fatal familial insomnia(FFI)cases usually displayed clinical symptoms earlier than genetic Creutzfeldt–Jakob disease(gCJD)patients with point mutations.A family history was more frequently recalled in P105L GSS and D178N FFI patients than T188K and E200K patients.None of the E196A gCJD patients reported a family history.The gCJD cases with point mutations always developed clinical manifestations typical of sporadic CJD(sCJD).EEG examination was not sensitive for gPrDs.sCJD-associated abnormalities on MRI were found in high proportions of GSS and gCJD patients.CSF 14-3-3 positivity was frequently detected in gCJD patients.Increased CSF tau was found in more than half of FFI and T188K gCJD cases,and an even higher proportion of E196A and E200K gCJD patients.63.6%of P105L GSS cases showed a positive reaction in cerebrospinal fluid RT-QuIC.GSS and FFI cases had longer durations than most subtypes of gCJD.This is one of the largest studies of gPrDs in East Asians,and the illness profile of Chinese gPrDs is clearly distinct.Extremely high proportions of T188K and E196A occur among Chinese gPrDs;these mutations are rarely reported in Caucasians and Japanese.