本文選題：肝豆狀核變性　切入點：兒童　出處：《青島大學》2017年碩士論文

【摘要】：目的對肝豆狀核變性(hepatolenticular degeneration,HLD)患者的臨床資料進行總結分析,了解HLD患者的基因突變類型及治療方法,進一步豐富HLD患者臨床資料,提高診斷率,總結有效的治療方法,以期對臨床醫(yī)生有指導作用。方法回顧性分析我院近3年收治的10例肝豆狀核變性患者的臨床資料、實驗室檢查結果、治療及隨訪,并對患者及其父母應用DNA一代測序檢測ATP7B基因(21個外顯子編碼區(qū)及內(nèi)含子—外顯子交界處),進行基因診斷。結果本研究共有10例患者,其中男4例,女6例,無陽性家族史。對其首發(fā)癥狀進行統(tǒng)計:肝功能異常為主者5例,神經(jīng)系統(tǒng)癥狀為主者2例,血液系統(tǒng)疾病為主者2例,肝功能異常合并神經(jīng)系統(tǒng)癥狀為1例。10例患者24h尿銅指標均高于正常值,銅藍蛋白含量均低于0.08g/L;10例HLD患者檢查角膜K-F環(huán),7例出現(xiàn)陽性;對10例HLD患者的肝、脾、腎等器官進行超聲檢查,發(fā)現(xiàn)10例患者中6例患者出現(xiàn)肝腫大,1例患者出現(xiàn)肝硬化,5例患者出現(xiàn)脾腫大,1例患者出現(xiàn)腎臟錯構瘤;尿液分析檢查2例患者出現(xiàn)蛋白尿,2例患者出現(xiàn)血尿。顱腦MRI檢查10例患者,發(fā)現(xiàn)1例患者腦部存在異常,表現(xiàn)為雙側豆狀核、尾狀核、腦橋多發(fā)異常信號。本研究對10例患者及父母的ATP7B基因全外顯子的編碼區(qū)進行DNA一代測序,10例確診為HLD的患者中均發(fā)現(xiàn)ATP7B基因存在突變,共發(fā)現(xiàn)9種基因突變,包括1種剪接突變、1種無義突變(p.Arg1319*)和7種錯義突變(p.Arg778Leu、p.Ala874Val、p.Pro992Leu、p.Asn1270Ser、p.Pro840Leu、p.Thr935Met、p.Asp1047Val)。本研究中檢出的基因突變均為雜合突變,5例患者均存在8號外顯子p.Arg778Leu突變;3例患者均存在13號外顯子p.Pro992Leu突變,基因突變頻率分別為25%、15%。根據(jù)本研究可以認為,本地區(qū)ATP7B基因的高頻突變位點是8號外顯子第778密碼子(R778L),其次為第13號外顯子第992密碼子(P992L)。針對10例患者的不同情況,采用二巰丙磺酸鈉注射液、硫酸鋅、青霉胺進行驅(qū)銅治療及保肝治療,結合肝功能檢查、24小時尿銅等隨訪指標,10例患者的病情的得到控制并趨于平穩(wěn)。結論1、不明原因的肝病和(或)神經(jīng)系統(tǒng)異常、脾腫大、黃疸、溶血性貧血、腎臟損害,需考慮本病的可能。綜合患者銅藍蛋白、角膜K-F環(huán)、24小時尿銅,并結合臨床表現(xiàn)及肝、腦等影像學檢查,可以做出臨床確診。2、本地區(qū)HLD患者ATP7B基因的高頻突變位點是8號外顯子第778密碼子(R778L),其次為第13號外顯子第992密碼子(P992L)。3、該研究表明對HLD患者采取驅(qū)銅及保肝治療是行之有效的。
[Abstract]:Objective to summarize and analyze the clinical data of patients with hepatolenticular degenerationHLD (hepatolenticular degenerationHLD), to understand the type of gene mutation and the treatment methods in HLD patients, to enrich the clinical data of HLD patients, to improve the diagnostic rate, and to summarize the effective treatment methods.With a view to clinical doctors have a guiding role.Methods the clinical data, laboratory findings, treatment and follow-up of 10 patients with hepatolenticular degeneration were retrospectively analyzed.DNA generation sequencing was used to detect the ATP7B gene (21 exon coding regions and intron-exon junction) in patients and their parents for gene diagnosis.Results A total of 10 patients, including 4 males and 6 females, had no positive family history.The initial symptoms were as follows: 5 cases with abnormal liver function, 2 cases with nervous system symptoms, 2 cases with hematological diseases, 5 cases with abnormal liver function, 2 cases with nervous system symptoms and 2 cases with hematological diseases.The urine copper index of 10 patients with abnormal liver function and nervous system symptom was higher than normal value, the content of ceruloplasmin was lower than 0.08g / L in 10 patients with HLD, 7 patients were positive for K-F loop of cornea, 10 patients with HLD had liver, spleen, liver, spleen, liver, spleen, liver, spleen, liver, spleen, liver, spleen, liver, spleen, liver, spleen, liver and spleen.Ultrasound examination of kidney and other organs showed that 6 out of 10 patients had hepatomegaly and 1 patient had cirrhosis and 5 patients had splenomegaly and 1 patient had renal hamartoma.Urine analysis was performed in 2 patients with proteinuria and 2 patients with hematuria.Brain MRI examination in 10 cases showed that 1 patient had abnormal brain signals, including bilateral lentiform nucleus, caudate nucleus and pontine multiple abnormal signals.In this study, 10 patients and their parents' ATP7B gene were sequenced by DNA generation sequencing. In 10 patients with HLD, 9 mutations were found in ATP7B gene.鍖呮嫭1縐嶅壀鎺ョ獊鍙，

本文編號：1702689