本文選題：多種�；o酶A脫氫酶缺乏癥 + 核黃素反應(yīng)性脂質(zhì)沉積性肌病��； 參考：《南昌大學(xué)》2017年碩士論文

【摘要】：背景與目的:中性脂肪沉積癥伴肌病(neutral lipid storage disease with myopathy,NLSDM)是一種少見(jiàn)的常染色體隱性遺傳的脂肪代謝障礙性疾病,是由于patatin樣磷酸脂酶結(jié)構(gòu)域蛋白(PNPLA2)基因突變導(dǎo)致甘油三酯分解障礙所致。核黃素反應(yīng)性脂質(zhì)沉積性肌病(riboflavin responsive multiple Acyl-CoA dehydrogenation deficiency,RR-MADD)是一種常染色體隱性遺傳性脂代謝通路障礙性病,主要是由電子轉(zhuǎn)移黃素蛋白脫氫酶基因(ETFDH)突變所致。肌肉活檢病理檢查發(fā)現(xiàn)這兩類脂肪沉積性肌病患者的肌纖維內(nèi)都有大量脂滴沉積,不同的是在大多數(shù)NLSDM患者的肌纖維中可以發(fā)現(xiàn)許多大小不等的脂質(zhì)沉積空泡,部分患者伴隨出現(xiàn)鑲邊空泡;而大多數(shù)RR-MADD患者中肌纖維內(nèi)也出現(xiàn)大量細(xì)小脂質(zhì)空泡,常常伴隨肌纖維壞死變性。上述不同的病理改變提示這兩類疾病的發(fā)病機(jī)制有所不同。因而有必要在總結(jié)上述兩種脂質(zhì)代謝障礙性疾病的臨床和病理的基礎(chǔ)上,對(duì)他們可能的病理發(fā)生機(jī)制進(jìn)一步進(jìn)行研究。為此我們報(bào)道江西地區(qū)8例RR-MADD和4例NLSDM患者的臨床表現(xiàn)、病理表現(xiàn),以及探討可能的發(fā)病機(jī)制。材料與方法:選取2011年4月至2016年4月就診于南昌大學(xué)第一附屬醫(yī)院神經(jīng)內(nèi)科的患者,行肌肉活檢+冰凍酶組織化學(xué)染色及基因檢查證實(shí)為脂質(zhì)沉積性肌病的12例患者,其中8例為核黃素反應(yīng)性脂質(zhì)沉積性肌病、4例為中性脂肪沉積癥伴肌病患者的臨床、病理資料進(jìn)行分析,行免疫熒光檢測(cè)自噬及凋亡相關(guān)蛋白的表達(dá)。結(jié)果:1、8例RR-MADD患者,其中7例為散發(fā),1例有家族史,臨床表現(xiàn)主要為四肢近端肌無(wú)力、不能耐受疲勞、肌酸脹為特征,2例患者有進(jìn)食后嘔吐發(fā)生,2例患者有肢體麻木、感覺(jué)性共濟(jì)失調(diào),給予核黃素治療肌無(wú)力臨床癥狀有明顯的改善。4例NLSDM患者,均為散發(fā),臨床表現(xiàn)主要為不對(duì)稱性四肢近端肌無(wú)力,伴心臟受累,目前還未有特效的治療藥物。2、8例RR-MADD患者,肌肉活檢均顯示肌纖維內(nèi)大量脂滴沉積,以Ⅰ肌纖維為主,2例患者肌纖維出現(xiàn)較多壞死改變。4例NLSDM患者,肌纖維內(nèi)有大量脂滴沉積,均出現(xiàn)數(shù)量不等的鑲邊空泡,同時(shí)肌纖維出現(xiàn)肥大萎縮和結(jié)締組織增生。3、8例RR-MADD患者,免疫熒光顯示肌纖維內(nèi)出現(xiàn)Bax、Caspase-3凋亡誘導(dǎo)蛋白在病變肌纖維內(nèi)聚集表達(dá),而抗凋亡蛋白(Bcl-2)無(wú)明顯表達(dá)變化。4例NLSDM患者,免疫熒光顯示肌纖維內(nèi)出現(xiàn)LC3和P62自噬蛋白聚集高表達(dá),肌纖維內(nèi)出現(xiàn)Bax、Caspase-3凋亡蛋白無(wú)明顯聚集表達(dá)。結(jié)論:1、RR-MADD和NLSDM這兩類脂質(zhì)沉積性肌病的臨床存在較大的差異性,RR-MADD主要表現(xiàn)為對(duì)稱性的肢體近端無(wú)力,多表現(xiàn)為肌無(wú)力癥狀的波動(dòng)和疲勞現(xiàn)象,伴隨胃腸道或周圍神經(jīng)癥狀;NLSDM主要表現(xiàn)為不對(duì)稱性肢體和軀干無(wú)力,無(wú)癥狀的波動(dòng)性,伴隨心肌或糖尿病。2、RR-MADD和NLSDM的病理改變?cè)诩膊〉闹泻笃诖嬖谝欢ǖ牟町愋?RR-MADD主要為肌纖維的壞死和變性,NLSDM主要為肌纖維的萎縮肥大,以及鑲邊空泡改變。3、RR-MADD的病變肌纖維通過(guò)凋亡通路走向肌纖維變性;NLSDM的病變肌纖維通過(guò)自噬通路走向肌纖維變性。
[Abstract]:Background and objective: neutral fat deposition disease associated with myopathy (neutral lipid storage disease with myopathy, NLSDM) is the fat metabolic disorder is a rare autosomal recessive, is due to patatin like phospholipase domain protein (PNPLA2) gene mutation caused by the disorder caused by decomposition of triglyceride. Riboflavin responsive lipid storage myopathy (riboflavin responsive multiple Acyl-CoA dehydrogenation deficiency, RR-MADD) is an autosomal recessive disorder of lipid metabolism pathway of sexually transmitted diseases, mainly Huang Sudan butter hydrogenase by electron transfer gene (ETFDH) mutation. Muscle biopsy pathology showed that these two kinds of fat storage myopathy patients in skeletal muscle fibers have a large number of lipid droplets. Is different in most NLSDM muscle fibers can be many different size lipid vacuoles were found, some patients with The muscle fibers showing rimmed vacuoles; in most patients with RR-MADD also appeared in a large number of small lipid vacuoles, often accompanied by necrosis of muscle fiber degeneration. The different pathological changes of the pathogenesis of these two diseases that are different. So it is necessary to summarize the clinical and pathological basis of the above two kinds of lipid metabolism disorders on the mechanism they may occur on the pathology of further study. We report the clinical manifestations, 8 cases of RR-MADD in Jiangxi area and 4 cases of NLSDM patients with pathological findings, and to explore the possible pathogenesis. Materials and methods: from April 2011 to April 2016 in the First Affiliated Hospital of Nanchang University with muscle biopsy + frozen tissue enzyme chemical staining and gene examination confirmed 12 cases of lipid storage myopathy patients, including 8 cases of riboflavin responsive lipid storage myopathy, 4 cases The neutral fat deposition in patients with myopathy with clinical, pathological data were detected by immunofluorescence analysis, expression of autophagy and apoptosis related proteins. Results: 1,8 RR-MADD patients, including 7 cases of sporadic, 1 cases with family history, the major clinical manifestations of proximal limb weakness, can not tolerate fatigue, swelling characteristics of creatine, 2 patients had vomiting after eating, 2 patients with limb numbness, sensory ataxia, giving riboflavin treatment significantly improved clinical symptoms of myasthenia gravis.4 NLSDM patients were sporadic, the major clinical manifestations of the asymmetry of the proximal limb weakness, with heart involvement, there is no specific treatment for.2,8 RR-MADD patients, muscle biopsy showed muscle fibers in a large number of lipid droplets deposition in muscle fibers, 1, 2 patients have more muscle fiber necrosis.4 NLSDM patients, the muscle fibers within a large number of lipid droplets, which are The number of rimmed vacuoles, muscle fibers atrophy and hypertrophy and hyperplasia of connective tissue of.3,8 patients with RR-MADD, immunofluorescence showed Bax in skeletal muscle fibers, Caspase-3 apoptosis inducing protein aggregation expression in lesions in skeletal muscle fibers, and anti apoptotic protein (Bcl-2) had no obvious changes in the expression of.4 in patients with NLSDM, immunofluorescence showed muscle the fiber LC3 and autophagy protein P62 aggregation high expression of Bax in skeletal muscle fibers, no obvious aggregation of Caspase-3 apoptosis protein expression. Conclusion: 1. Clinical RR-MADD and NLSDM these two kinds of lipid storagemyopathy differences, RR-MADD showed symmetric proximal limb weakness, showed more fluctuation and the phenomenon of fatigue symptoms of myasthenia gravis, accompanied by gastrointestinal symptoms or peripheral nerve; NLSDM mainly for the asymmetry of the limbs and trunk weakness, the volatility of asymptomatic, or diabetes associated with myocardial.2, RR-MADD The pathological changes in NLSDM, there are some differences in the disease in late RR-MADD, mainly for muscle fiber necrosis and degeneration of NLSDM, mainly for hypertrophy of muscle fiber atrophy, and rimmed vacuoles change.3 lesions, muscle fiber RR-MADD through apoptosis pathway to muscle fiber degeneration; muscle fiber lesions by NLSDM of the autophagy pathway to muscle fiber degeneration.

【學(xué)位授予單位】：南昌大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R589.2

【參考文獻(xiàn)】

相關(guān)期刊論文 前7條

1 李務(wù)榮;楊旭;趙丹華;洪道俊;袁云;鄭日亮;張巍;王朝霞;;核黃素反應(yīng)性脂質(zhì)沉積性肌病伴感覺(jué)共濟(jì)失調(diào)性神經(jīng)病3例報(bào)告[J];中風(fēng)與神經(jīng)疾病雜志;2012年03期

2 奚劍英;盧家紅;趙重波;林潔;羅蘇珊;朱雯華;喬凱;黃俊;汪寅;;脂質(zhì)沉積性肌病35例的臨床特點(diǎn)及電子轉(zhuǎn)移黃素蛋白脫氫酶基因突變分析[J];中華神經(jīng)科雜志;2011年05期

3 吳志英;王檸;;我國(guó)核黃素反應(yīng)性脂質(zhì)沉積性肌病基因研究的現(xiàn)狀及熱點(diǎn)問(wèn)題[J];中華神經(jīng)科雜志;2011年05期

4 王韻;趙丹華;洪道俊;王朝霞;袁云;;核黃素反應(yīng)性脂質(zhì)沉積性肌病20個(gè)家系的電子轉(zhuǎn)移黃素蛋白脫氫酶基因存在熱點(diǎn)突變[J];中華神經(jīng)科雜志;2011年05期

5 王勤周,焉傳祝,吳金玲,劉淑萍,高素琴,李偉,李大年;核黃素反應(yīng)性脂質(zhì)沉積性肌病的臨床和病理特征[J];臨床神經(jīng)病學(xué)雜志;2005年05期

6 陳涓涓;洪道俊;張巍;王朝霞;袁云;;中性脂肪沉積癥合并肌病一家系[J];中華神經(jīng)科雜志;2009年09期

7 曹佩芝;呂丹云;夏謙;吳淑平;;脂質(zhì)沉積性肌病二例報(bào)告[J];中華精神科雜志;1990年04期

，

本文編號(hào)：1756285