A Case Of Transthyretin-type Familial Amyloid Polyneuropathy Caused By F84S And Reported Cases Retrospective Analysis

Background:Transthyretin-type familial amyloid polyneuropathy(ATTR-FAP)which is an autosomal dominant inheritance,also known as hereditary amyloidosis,it is a rare systemic disease characterized by irreversible progressive peripheral nerve injury,mostly caused by transthyretin(TTR)gene mutation.At present,20 kinds of TTR gene mutations have been found in China,mainly distributed in the Han nationality.Objective:This article will report a case of TTR-F84S mutation caused by central nervous system involvement as a special manifestation of FAP,and summarize its clinical manifestations,neuromuscular electrophysiology and histopathological features.The characteristics and influencing factors of FAP clinical manifestations were discussed by searching the reported familial amyloid peripheral nerve data.Methods:The detailed clinical data of a patient with amyloid peripheral neuropathy caused by TTR gene mutation were collected.The TTR gene was detected by PCR and DNA amplification technology,and its clinical characteristics were analyzed.The reported TTR gene-associated amyloid peripheral neuropathy cases were then collected by a search database,and clinical manifestations were extracted and analyzed.Results:1.Mutations in the TTR gene can cause central nervous system symptoms.The first symptoms are mostly peripheral neurological symptoms,stroke-like symptoms,decreased vision,headache,nausea,vomiting,etc.A small number of patients have psychiatric symptoms or subarachnoid hemorrhage or epilepsy as the first symptom.2.F84S is a FAP pathogenic mutation characterized by central nervous system involvement.The clinical features of this case are:early-onset FAP mostly onset with gastrointestinal symptoms(nausea,vomiting)and autonomic symptoms,combined with ocular involvement to peripheral nerves Symptoms of damage(especially autonomic symptoms)are most prominent.There is only one family report about same mutation in foreign countries.The cases described in this report have central nervous system,peripheral nervous system and heart,kidney and eye involvement,and are prominent in central involvement(intracranial hemorrhage,epilepsy,hemiplegia,etc.).3.A total of 112 articles and 169 patients with ATTR-FAP were enrolled in this study.Statistical analysis was performed:(1)There is a significant racial difference between central nervous system symptoms and age at onset due to TTR mutations.Patients with early onset(31.8%)were more likely to have central damage(14.3%,P=0.014,coefficient of contingency=0.197);Caucasians(31.6%)were older than yellow(17.4%)(?~2=4.295,P=0.038,coefficient of contingency=0.158).There was no significant correlation between the incidence of central damage symptoms and gender differences(24.8%for males,28.8%for females,2=0.308,P=0.579).(2)FAP male and female distribution was about 2:1,and there was no significant correlation between age of onset and gender(?2=0.007,P=0.935).There was a significant racial difference in the first clinical manifestations.The yellow race(24.6%)was more likely to have autonomic symptoms than the Caucasian(7.6%);the Caucasian(11.4%)was more likely to have heart symptoms than the yellow(6.6%).(?2=10.479,P=0.033,coefficient of contingency=0.303).The first symptom was significantly associated with the age of onset.The first symptoms of early onset and late onset had the most common peripheral nerve damage.However,the first symptom was autonomic and gastrointestinal symptoms more likely to occur in early-onset patients;the first symptom of cardiac symptoms is more likely to occur in patients with late-onset(?2=24.908,P=0.000,coefficient of contingency=0.395).Conclusion:1.F84S mutation is a pathogenic mutation of FAP.The clinical features are:first symptom is gastrointestinal symptoms(nausea,vomiting)and autonomic symptoms;central nervous system involvement is a special manifestation of early-onset FAP;can be combined with other system involvement symptom.2.FAP patients are more male than female,about 2:1.Yellow people are more likely to have early-onset FAP,early-onset patients are more likely to have autonomic and gastrointestinal symptoms than late-onset patients,and late-onset patients are more likely Onset of heart symptoms.Central system involvement is more likely to occur in early-onset patients.