Objective To study the characteristics of spectra on proton magnetic resonance spectroscopy （^1H-MRS） and its value in patients with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes （ME...Objective To study the characteristics of spectra on proton magnetic resonance spectroscopy （^1H-MRS） and its value in patients with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes （MELAS）. Methods Seven clinically diagnosed patients with MELAS underwent magnetic resonance imaging （MRI） and ^1H-MRS examinations. The ^1H-MRS techniques, characteristics of the spectra, and its correlation with the laboratory tests were analyzed. Reaults Cerebral abnormalities were revealed in all 7 patients on conventional MR images, and most abnormal signals were observed in bilateral occipital, parietal, and temporal lobes. We found 4 cases with basal ganglia involvement, 2 cases with mild frontal lobe lesions, and 1 case with involvement of lateral cerebral peduncles and thalami. Additionally, 1 patient was involved with left insular lobe. Spectra from prominent lesions in brain parenchyma showed lactate doublet peak in 6 patients, 3 of whom were also noted lactate peak in ventricular cerehrospinal fluid （CSF）. Conclusion ^1H-MRS may provide more direct information about the metabolism changes, which aids to affirm the diagnosis, and may replace the conventional invasive method of quantifying lactate in CSF.展开更多
Objective To search for A3243G point mutations in mitochondrial DNA (mtDNA) from 10 cases of mitochondrial encephalomyopathy, lactic acidosis and strokelike episodes (MELAS) Methods Using PCR restriction analysis,...Objective To search for A3243G point mutations in mitochondrial DNA (mtDNA) from 10 cases of mitochondrial encephalomyopathy, lactic acidosis and strokelike episodes (MELAS) Methods Using PCR restriction analysis, we investigated A3243G point mutations in mtDNA of muscle and/or blood cells from 10 patients and their 8 maternal relatives We also quantitated the A3243G mtDNA in samples harboring the mutation Results A3243G point mutations were identified in all muscle and/or blood samples from 10 MELAS patients The proportion of mutant mtDNA was 10 8%-47 8% in blood (7 cases), and 39 4%-67 7% in muscle (5 cases) This ratio was invariably higher in muscle than in blood from two patients whose blood and muscle samples were both available Younger patients usually carried higher proportions of A3243G mutant mtDNA in blood Eight maternal relatives from 6 families were also examined Maternal transmission of the disease could be identified in one family No A3243G point mutations were found in mothers' blood from 3 families and siblings' blood from 2 families Conclusions All 10 MELAS patients were found to have the mtDNA A3243G mutation in their muscle and/or blood The A3243G mutation seems to be sporadic in 5 of the families examined, suggesting the mechanism of de novo mutation for the pathogenesis of their MELAS syndrome展开更多
Mitochondrial encephalomyopathy with lactic acidosis and strokelike episodes (MELAS) is a metabolic disorder characterized by hyperlactic acidemia and stroke-like symptoms.
To the Editor: Mitochondrial encephalomyopathy with lactate acidosis and stroke-like episodes (MELAS) is one of the most common multisystem mitochondrial disorders with broad clinical manifestations.[1] It is usually ...To the Editor: Mitochondrial encephalomyopathy with lactate acidosis and stroke-like episodes (MELAS) is one of the most common multisystem mitochondrial disorders with broad clinical manifestations.[1] It is usually caused by point mutations in the mitochondrial MT-TL1 gene, which accounts for approximately 80% of mutations in individuals with MELAS syndrome.[2] Pathogenic mitochondrial DNA (mtDNA) mutations were first described in 1980[3] and m.l4487T>C is a known pathogenic mtDNA mutation,[4] which has been reported in patients with Leigh syndrome, optic neuropathy, ptosis, dystonia, and encephalomyopathy. We herein report a patient with late-onset MELAS syndrome with the m.l4487T>C mutation for the first time.展开更多
The first description of a syndrome including stroke-like episodes, lactic acidaemia, and ragged red fibres, was reported by Shapira et al in 1975. 1 Pavlakis et al 2 described further cases, introduced the acr...The first description of a syndrome including stroke-like episodes, lactic acidaemia, and ragged red fibres, was reported by Shapira et al in 1975. 1 Pavlakis et al 2 described further cases, introduced the acronym MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes), and suggested that this represented a distinct mitochondrial disease phenotype. In 1990, Goto et al 3 identified A3243G mutation in the transfer RNA (tRNA) leucine (UUR) gene in some patients with MELAS. Although this mutation has now been established to be the commonest mtDNA defect it is often misdiagnosed. Here we report a kindred of MELAS including a mother and a son. Clinical, pathological and genetic studies are proceeding.展开更多
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes （MELAS） are common types of mitochondrial encephalomyopathy. The involved muscular pathology is characterized by typical changes of mitochon...Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes （MELAS） are common types of mitochondrial encephalomyopathy. The involved muscular pathology is characterized by typical changes of mitochondrial abnormalities. Gene screening has been the gold diagnostic standard for MELAS diagnosis. This study presents three primary MELAS patients, with an age of onset from 13 to 18 years, including one patient with seizure, and two with headache and vomiting. All patients had a family history of disease, with maternal inheritance. Cerebral magnetic resonance imaging revealed abnormally high signals in T2-weighted images： temporal lobe in three cases, occipital lobe in two cases, and parietal lobe in one case. Migrating stroke-like lesions were confirmed in one patient. Muscle biopsy revealed several strongly succinate dehydrogenase-reactive vessels scattered in muscle sections of three patients, but ragged-red fibers and cytochrome c oxidase-negative/dense （COX-/＋） fibers were not observed. Mitochondrial DNA A3243G mutation was identified in all three cases. MELAS syndrome has obvious clinical heterogeneity, and muscle weakness was not prominent in some of the cases. Muscle pathological changes did not accompany ragged-red fibers or COX-/＋ fibers, but succinate dehydrogenase- reactive vessels are important for MELAS diagnosis.展开更多
BACKGROUND Mitochondrial encephalomyopathy(ME)is a multisystem metabolic disease that primarily affects the central nervous system and skeletal muscle.It is caused by mutations in mitochondrial or nuclear DNA,resultin...BACKGROUND Mitochondrial encephalomyopathy(ME)is a multisystem metabolic disease that primarily affects the central nervous system and skeletal muscle.It is caused by mutations in mitochondrial or nuclear DNA,resulting in abnormal mitochondrial structure and function and insufficient ATP synthesis.The most common subtype is mitochondrial encephalomyopathy,lactic acidosis,and stroke-like episode(MELAS)syndrome.In recent years,reports of MELAS syndrome have increased but familial cases are rare.CASE SUMMARY We report a case of familial MELAS syndrome.Cases 2 and 3 are sisters and case 1 is their nephew.All are short in stature and showed stroke-like episodes with rapid onset and no obvious symptoms such as paroxysmal headache,aphasia,or blurred vision.After admission,blood lactate levels were significantly higher than normal.The patients underwent magnetic resonance imaging of the head.Cases 1 and 2 were considered to have ME,whereas case 3 was considered to have a space-occupying lesion in the left temporal lobe.Pathological evaluation showed no obvious tumor cells in the brain lesions of case 3.Muscle biopsy or genetic test results were consistent with ME.The patients were diagnosed with MELAS syndrome and their symptoms improved with intravenous infusions of coenzyme Q10,coenzyme A,vitamin B,and vitamin C.At the 6 mo follow-up,there was no recurrence or progression.CONCLUSION When a patient has MELAS syndrome,familial MELAS syndrome should be considered if related family members have similar symptoms.展开更多
目的提高临床医师对线粒体脑肌病伴高乳酸血症和卒中样发作综合征(mitochondrial encephalomyopathy with lactic academia and stroke-like episodes,MELAS)的认识,以早期诊断及治疗,改善患者预后。方法结合MELAS既往的文献报道,总结ME...目的提高临床医师对线粒体脑肌病伴高乳酸血症和卒中样发作综合征(mitochondrial encephalomyopathy with lactic academia and stroke-like episodes,MELAS)的认识,以早期诊断及治疗,改善患者预后。方法结合MELAS既往的文献报道,总结MELAS患者的临床表现、实验室及影像学检查、病理特点、基因检测、诊断标准及鉴别诊断、治疗与预后情况。结果MELAS患者主要表现为运动不耐受、卒中样发作、癫痫、失明、眼外肌瘫痪、听力下降、癫痫,肌酸激酶正常或者增高,运动后血乳酸增高。肌肉活检见破碎红纤维(RRF)和SDH染色肌间小血管强染(SSV),ATP酶染色可见肌纤维呈棋盘格样分布,HE染色可见边缘嗜碱性肌纤维。头MRI表现皮层卒中样改变、脑萎缩。结论 MELAS患者主要以脑和肌肉受累为主要临床表现,RRF、SSV、肌纤维呈棋盘格样分布、嗜碱性肌纤维为肌肉活检的主要特点。展开更多
文摘Objective To study the characteristics of spectra on proton magnetic resonance spectroscopy （^1H-MRS） and its value in patients with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes （MELAS）. Methods Seven clinically diagnosed patients with MELAS underwent magnetic resonance imaging （MRI） and ^1H-MRS examinations. The ^1H-MRS techniques, characteristics of the spectra, and its correlation with the laboratory tests were analyzed. Reaults Cerebral abnormalities were revealed in all 7 patients on conventional MR images, and most abnormal signals were observed in bilateral occipital, parietal, and temporal lobes. We found 4 cases with basal ganglia involvement, 2 cases with mild frontal lobe lesions, and 1 case with involvement of lateral cerebral peduncles and thalami. Additionally, 1 patient was involved with left insular lobe. Spectra from prominent lesions in brain parenchyma showed lactate doublet peak in 6 patients, 3 of whom were also noted lactate peak in ventricular cerehrospinal fluid （CSF）. Conclusion ^1H-MRS may provide more direct information about the metabolism changes, which aids to affirm the diagnosis, and may replace the conventional invasive method of quantifying lactate in CSF.
文摘Objective To search for A3243G point mutations in mitochondrial DNA (mtDNA) from 10 cases of mitochondrial encephalomyopathy, lactic acidosis and strokelike episodes (MELAS) Methods Using PCR restriction analysis, we investigated A3243G point mutations in mtDNA of muscle and/or blood cells from 10 patients and their 8 maternal relatives We also quantitated the A3243G mtDNA in samples harboring the mutation Results A3243G point mutations were identified in all muscle and/or blood samples from 10 MELAS patients The proportion of mutant mtDNA was 10 8%-47 8% in blood (7 cases), and 39 4%-67 7% in muscle (5 cases) This ratio was invariably higher in muscle than in blood from two patients whose blood and muscle samples were both available Younger patients usually carried higher proportions of A3243G mutant mtDNA in blood Eight maternal relatives from 6 families were also examined Maternal transmission of the disease could be identified in one family No A3243G point mutations were found in mothers' blood from 3 families and siblings' blood from 2 families Conclusions All 10 MELAS patients were found to have the mtDNA A3243G mutation in their muscle and/or blood The A3243G mutation seems to be sporadic in 5 of the families examined, suggesting the mechanism of de novo mutation for the pathogenesis of their MELAS syndrome
基金Support Projects of“Yangfan Plan”of Beijing Medical Administration (No.ZYLX201836)National Natural Science Foundation of China (No.NSFC81371201)+4 种基金Key projects of basic and clinical cooperation of Capital Medical University (No.16JL03)National Key Technology Research and Development Program of the Ministry of Science and Technology of The People's Republic of China (No.2015BAI12B04)National Key Technology Research and Developmenr Program of the Ministry of Science and Technology of The People's Republic of China (No.2015BAI12B02)Beijing Institute For Brain Disorders (No.1152130306)Beijing Municipal Administration of Hospitals' Mission Plan (No.SML20150502).
文摘Mitochondrial encephalomyopathy with lactic acidosis and strokelike episodes (MELAS) is a metabolic disorder characterized by hyperlactic acidemia and stroke-like symptoms.
基金grants from the National Natural Science Foundation of China (No. 81671235 and No. 81701237)People's Benefit Project of Science and Technology in Qingdao (No. 16-6-2-1-nsh) and the Taishan Scholars Program of Shandong Province.
文摘To the Editor: Mitochondrial encephalomyopathy with lactate acidosis and stroke-like episodes (MELAS) is one of the most common multisystem mitochondrial disorders with broad clinical manifestations.[1] It is usually caused by point mutations in the mitochondrial MT-TL1 gene, which accounts for approximately 80% of mutations in individuals with MELAS syndrome.[2] Pathogenic mitochondrial DNA (mtDNA) mutations were first described in 1980[3] and m.l4487T>C is a known pathogenic mtDNA mutation,[4] which has been reported in patients with Leigh syndrome, optic neuropathy, ptosis, dystonia, and encephalomyopathy. We herein report a patient with late-onset MELAS syndrome with the m.l4487T>C mutation for the first time.
基金ThisworkwassupportedbythegrantsfromtheGuangdongNaturalScienceFoundationProgram (No 31694 )andtheGuangdongNaturalScienceFoundationKeyProgram (No21894)
文摘The first description of a syndrome including stroke-like episodes, lactic acidaemia, and ragged red fibres, was reported by Shapira et al in 1975. 1 Pavlakis et al 2 described further cases, introduced the acronym MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes), and suggested that this represented a distinct mitochondrial disease phenotype. In 1990, Goto et al 3 identified A3243G mutation in the transfer RNA (tRNA) leucine (UUR) gene in some patients with MELAS. Although this mutation has now been established to be the commonest mtDNA defect it is often misdiagnosed. Here we report a kindred of MELAS including a mother and a son. Clinical, pathological and genetic studies are proceeding.
文摘Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes （MELAS） are common types of mitochondrial encephalomyopathy. The involved muscular pathology is characterized by typical changes of mitochondrial abnormalities. Gene screening has been the gold diagnostic standard for MELAS diagnosis. This study presents three primary MELAS patients, with an age of onset from 13 to 18 years, including one patient with seizure, and two with headache and vomiting. All patients had a family history of disease, with maternal inheritance. Cerebral magnetic resonance imaging revealed abnormally high signals in T2-weighted images： temporal lobe in three cases, occipital lobe in two cases, and parietal lobe in one case. Migrating stroke-like lesions were confirmed in one patient. Muscle biopsy revealed several strongly succinate dehydrogenase-reactive vessels scattered in muscle sections of three patients, but ragged-red fibers and cytochrome c oxidase-negative/dense （COX-/＋） fibers were not observed. Mitochondrial DNA A3243G mutation was identified in all three cases. MELAS syndrome has obvious clinical heterogeneity, and muscle weakness was not prominent in some of the cases. Muscle pathological changes did not accompany ragged-red fibers or COX-/＋ fibers, but succinate dehydrogenase- reactive vessels are important for MELAS diagnosis.
文摘BACKGROUND Mitochondrial encephalomyopathy(ME)is a multisystem metabolic disease that primarily affects the central nervous system and skeletal muscle.It is caused by mutations in mitochondrial or nuclear DNA,resulting in abnormal mitochondrial structure and function and insufficient ATP synthesis.The most common subtype is mitochondrial encephalomyopathy,lactic acidosis,and stroke-like episode(MELAS)syndrome.In recent years,reports of MELAS syndrome have increased but familial cases are rare.CASE SUMMARY We report a case of familial MELAS syndrome.Cases 2 and 3 are sisters and case 1 is their nephew.All are short in stature and showed stroke-like episodes with rapid onset and no obvious symptoms such as paroxysmal headache,aphasia,or blurred vision.After admission,blood lactate levels were significantly higher than normal.The patients underwent magnetic resonance imaging of the head.Cases 1 and 2 were considered to have ME,whereas case 3 was considered to have a space-occupying lesion in the left temporal lobe.Pathological evaluation showed no obvious tumor cells in the brain lesions of case 3.Muscle biopsy or genetic test results were consistent with ME.The patients were diagnosed with MELAS syndrome and their symptoms improved with intravenous infusions of coenzyme Q10,coenzyme A,vitamin B,and vitamin C.At the 6 mo follow-up,there was no recurrence or progression.CONCLUSION When a patient has MELAS syndrome,familial MELAS syndrome should be considered if related family members have similar symptoms.
文摘目的提高临床医师对线粒体脑肌病伴高乳酸血症和卒中样发作综合征(mitochondrial encephalomyopathy with lactic academia and stroke-like episodes,MELAS)的认识,以早期诊断及治疗,改善患者预后。方法结合MELAS既往的文献报道,总结MELAS患者的临床表现、实验室及影像学检查、病理特点、基因检测、诊断标准及鉴别诊断、治疗与预后情况。结果MELAS患者主要表现为运动不耐受、卒中样发作、癫痫、失明、眼外肌瘫痪、听力下降、癫痫,肌酸激酶正常或者增高,运动后血乳酸增高。肌肉活检见破碎红纤维(RRF)和SDH染色肌间小血管强染(SSV),ATP酶染色可见肌纤维呈棋盘格样分布,HE染色可见边缘嗜碱性肌纤维。头MRI表现皮层卒中样改变、脑萎缩。结论 MELAS患者主要以脑和肌肉受累为主要临床表现,RRF、SSV、肌纤维呈棋盘格样分布、嗜碱性肌纤维为肌肉活检的主要特点。
