ミトコンドリア脳筋症・乳酸アシドーシス・脳卒中様発作症候群, mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike episodes, mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/09/30 10:05:06」(JST)

wiki ja

[Wiki ja表示]

ミトコンドリア脳筋症・乳酸アシドーシス・脳卒中様発作症候群 (Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, Stroke-like episodes)あるいは略してMELAS（メラス）は反復する脳卒中様発作を特徴とするミトコンドリア病の一種である（以下"MELAS"と呼ぶ）。MELASの80%がmtDNAの点突然変異（3243A→G変異）により引き起こされる。

症状

MELASの拡散強調画像。脳梗塞類似病変（白く見えるところ）を向かって左側に認める

MELASはミトコンドリアの障害でATP産生がうまくいかなくなるミトコンドリア病（ミトコンドリア脳筋症）の1種である。5～15歳で好発し、知能低下や感音性難聴、低身長、易疲労性、心筋症、筋力低下といったミトコンドリア病に共通する神経・筋症状のほかに、繰り返す脳卒中様発作（頭痛・嘔吐・痙攣・意識障害・片麻痺など）が特徴的で、この発作時にCTやMRI（拡散強調画像）をとると脳梗塞に類似した病変を認める（ただし、この病変の発症機序は不明）。

検査所見

MELASに伴う赤色ぼろ線維

ミトコンドリア病全般に共通することだが、ミトコンドリアでのATP産生（電子伝達系など）がうまくいかないことで解糖系が亢進し、血中・髄液中の乳酸濃度と乳酸/ピルビン酸比（L/P比）が上昇する。また、筋生検を行い、ゴモリ・トリクローム染色を行うと赤色ぼろ線維を認める。MELASに特徴的な所見としては、後頭部の脳梗塞類似病変や脳波での焦点周期性てんかん型放電がある。

遺伝

MELASの80%はミトコンドリアDNAの点変異(3243A→G)であり、母系遺伝する。

外部リンク

[1] - MELASの解説
[2] - MELASの解説
[3] - 頭痛に関する用語集（MELASの解説あり）
[4] - 難病情報センターによるMELASの解説
[5] - 「ミトコンドリア病患者へのコハク酸ナトリウムの投与」

この項目は、医学に関連した書きかけの項目です。この項目を加筆・訂正などしてくださる協力者を求めています（プロジェクト:医学／Portal:医学と医療）。

wiki en

[Wiki en表示]

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes – abbreviated to MELAS – is one of the family of mitochondrial cytopathies, which also include MERRF, and Leber's hereditary optic neuropathy. It was first characterized under this name in 1984.^[1] A feature of these diseases is that they are caused by defects in the mitochondrial genome which is inherited purely from the female parent.^[2] However, it is important to know that some of the proteins essential to normal mitochondrial function are produced by the nuclear genome, and are subsequently transported to the mitochondria for use. As such, mutations in these proteins can result in mitochondrial disorders, but can be inherited from both male and female parent in the typical fashion. The disease can manifest in both sexes.

Presentation

MELAS is a condition that affects many of the body's systems, particularly the brain and nervous system (encephalo-) and muscles (myopathy). In most cases, the signs and symptoms of this disorder appear in childhood following a period of normal development.^[3] Early symptoms may include muscle weakness and pain, recurrent headaches, loss of appetite, vomiting, and seizures. Most affected individuals experience stroke-like episodes beginning before age 40. These episodes often involve temporary muscle weakness on one side of the body (hemiparesis), altered consciousness, vision abnormalities, seizures, and severe headaches resembling migraines. Repeated stroke-like episodes can progressively damage the brain, leading to vision loss, problems with movement, and a loss of intellectual function (dementia). The stroke-like episodes can be mis-diagnosed as epilepsy by a doctor not aware of the MELAS condition.

Most people with MELAS have a buildup of lactic acid in their bodies, a condition called lactic acidosis. Increased acidity in the blood can lead to vomiting, abdominal pain, extreme tiredness (fatigue), muscle weakness, loss of bowel control, and difficulty breathing. Less commonly, people with MELAS may experience involuntary muscle spasms (myoclonus), impaired muscle coordination (ataxia), hearing loss, heart and kidney problems, diabetes, epilepsy, and hormonal imbalances.

The presentation of some cases is similar to that of Kearns-Sayre syndrome.^[4]

Genetics

Muscle biopsy of a person diagnosed with MELAS but carrying no known mutation. (a) Modified Gomori trichrome stain showing several ragged red fibers (arrowhead). (b) Cytochrome c oxidase stain showing Type-1 lightly stained and Type II fibers, darker fibers, and a few fibers with abnormal collections of mitochondria (arrowhead). Note cytochrome c oxidase negative fibers as usually seen in mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS). (c) Succinate dehydrogenase staining showing a few ragged blue fibers and intense staining in the mitochondria of the blood vessels (arrow). (d) Electron microscopy showing abnormal collection of mitochondria with paracrystalline inclusions (arrowhead), osmiophilic inclusions (large arrowhead) and mitochondrial vacuoles (small arrowhead). Abu-Amero et al. Journal of Medical Case Reports 2009.^[5]

MELAS is caused by mutations in the genes in mitochondrial DNA.

NADH dehydrogenase

Some of the genes (MT-ND1, MT-ND5) affected in MELAS encode proteins that are part of NADH dehydrogenase (also called complex I) in mitochondria, that helps convert oxygen and simple sugars to energy.

Transfer RNAs

Other genes (MT-TH, MT-TL1, and MT-TV) encode mitochondrial specific transfer RNAs (tRNAs).

Mutations in MT-TL1 cause more than 80 percent of all cases of MELAS. They impair the ability of mitochondria to make proteins, use oxygen, and produce energy. Researchers have not determined how changes in mitochondrial DNA lead to the specific signs and symptoms of MELAS. They continue to investigate the effects of mitochondrial gene mutations in different tissues, particularly in the brain.

Inheritance

This condition is inherited in a mitochondrial pattern, which is also known as maternal inheritance and heteroplasmy. This pattern of inheritance applies to genes contained in mitochondrial DNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, only females pass mitochondrial conditions to their children. Mitochondrial disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass mitochondrial traits to their children. In most cases, people with MELAS inherit an altered mitochondrial gene from their mother. Less commonly, the disorder results from a new mutation in a mitochondrial gene and occurs in people with no family history of MELAS.

Prognosis

There is no known treatment for the underlying disease, which is progressive and fatal. Patients are managed according to what areas of the body are affected at a particular time. Enzymes, amino acids, antioxidants and vitamins have been used, but there have been no consistent successes reported.

Although there have been no controlled trials on long-term benefits of dietary manipulations, the following supplements have shown promise and given hope to MELAS patients.

CoQ10 has been helpful for some MELAS patients.^[6] Nicotinamide has been used because complex l accepts electrons from NADH and ultimately transfers electrons to CoQ10.

Riboflavin has been reported to improve the function of a patient with complex l deficiency and the 3250T-C mutation.^[7]

The administration of L-arginine during the acute and interictal periods may represent a potential new therapy for this syndrome to reduce brain damage due to impairment of vasodilation in intracerebral arteries due to nitric oxide depletion.^[8]^[9]

There is also a case report where succinate was successfully used to treat uncontrolled convulsions in MELAS patients, although this treatment modality is yet to be thoroughly investigated or widely recommended.

References

^ Pavlakis SG, Phillips PC, DiMauro S, De Vivo DC, Rowland LP (1984). "Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes: a distinctive clinical syndrome". Ann Neurol 16 (4): 481–8. doi:10.1002/ana.410160409. PMID 6093682.
^ Hirano M, Pavlakis SG (1994). "Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS): current concepts". J Child Neurol 9 (1): 4–13. doi:10.1177/088307389400900102. PMID 8151079.
^ MELAS syndrome at NLM Genetics Home Reference
^ Hirano M, Ricci E, Koenigsberger MR, Defendini R, Pavlakis SG, DeVivo DC, DiMauro S, Rowland LP (1992). "Melas: an original case and clinical criteria for diagnosis". Neuromuscul Disord 2 (2): 125–35. doi:10.1016/0960-8966(92)90045-8. PMID 1422200.
^ Abu-Amero KK, Al-Dhalaan H, Bohlega S, Hellani A, Taylor RW (2009). "A patient with typical clinical features of mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) but without an obvious genetic cause: a case report". J Med Case Reports 3: 77. doi:10.1186/1752-1947-3-77. PMC 2783076. PMID 19946553.
^ Rodriguez MC, MacDonald JR, Mahoney DJ, Parise G, Beal MF, Tarnopolsky MA (2007). "Beneficial effects of creatine, CoQ10, and lipoic acid in mitochondrial disorders". Muscle Nerve 35 (2): 235–42. doi:10.1002/mus.20688. PMID 17080429.
^ Ogle RF, Christodoulou J, Fagan E, et al. (1997). "Mitochondrial myopathy with tRNA(Leu(UUR)) mutation and complex I deficiency responsive to riboflavin". J. Pediatr. 130 (1): 138–45. doi:10.1016/S0022-3476(97)70323-8. PMID 9003864.
^ Koga Y, Akita Y, Nishioka J, et al. (2007). "MELAS and L-arginine therapy". Mitochondrion 7 (1-2): 133–9. doi:10.1016/j.mito.2006.11.006. PMID 17276739.
^ Hirata K, Akita Y, Povalko N, et al. (2007). "Effect of l-arginine on synaptosomal mitochondrial function". Brain Dev 30 (4): 238. doi:10.1016/j.braindev.2007.08.007. PMID 17889473.

External links

melas at NIH/UW GeneTests

UpToDate Contents

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1. ミトコンドリアミオパシー：臨床的特徴および診断 mitochondrial myopathies clinical features and diagnosis
2. ミトコンドリアミオパシー：治療 mitochondrial myopathies treatment
3. 小児および若年成人における虚血性脳卒中：病因と臨床的特徴 ischemic stroke in children and young adults etiology and clinical features
4. 小児における虚血性脳卒中：評価、初期マネージメント、および予後 ischemic stroke in children evaluation initial management and prognosis
5. 乳酸アシドーシスの原因 causes of lactic acidosis

English Journal

Mitochondrial DNA mutations in diabetes mellitus patients in Chinese Han population.

Wang S, Wu S, Zheng T, Yang Z, Ma X, Jia W, Xiang K.SourceDepartment of Endocrinology and Metabolism, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, Henan 450003, China.
Gene.Gene.2013 Dec 1;531(2):472-5. doi: 10.1016/j.gene.2013.09.019. Epub 2013 Sep 19.
BACKGROUND AND OBJECTIVE: Mutations of mitochondrial DNA are associated with diabetes mellitus (DM). The present case-control study aimed to investigate the mutations of mitochondrial DNA in DM patients of Chinese Han ethnicity.METHODS AND RESULTS: A total of 770 DM patients and 309 healthy control
PMID 24055484

Respiratory complex III dysfunction in humans and the use of yeast as a model organism to study mitochondrial myopathy and associated diseases.

Meunier B, Fisher N, Ransac S, Mazat JP, Brasseur G.SourceCNRS, Centre de Génétique Moléculaire, UPR 3404, Gif-sur-Yvette, F-91198, France.
Biochimica et biophysica acta.Biochim Biophys Acta.2013 Nov-Dec;1827(11-12):1346-61. doi: 10.1016/j.bbabio.2012.11.015. Epub 2012 Dec 5.
The bc1 complex or complex III is a central component of the aerobic respiratory chain in prokaryotic and eukaryotic organisms. It catalyzes the oxidation of quinols and the reduction of cytochrome c, establishing a proton motive force used to synthesize adenosine triphosphate (ATP) by the F1Fo ATP
PMID 23220121

Characterization of swarming and mating behaviour between Anopheles coluzzii and Anopheles melas in a sympatry area of Benin.

Assogba BS, Djogbénou L, Saizonou J, Diabaté A, Dabiré RK, Gilles J, Makoutodé M, Baldet T.SourceInstitut Régional de Santé Publique, Université d'Abomey Calavi, 01BP918 Cotonou, Benin.
Acta tropica.Acta Trop.2013 Oct 7. pii: S0001-706X(13)00241-6. doi: 10.1016/j.actatropica.2013.09.006. [Epub ahead of print]
The swarm structure of two sibling species, Anopheles gambiae coluzzii and Anopheles melas, was characterize to explore the ecological and environmental parameters associated with the formation of swarms and their spatial distribution. Swarms and breeding sites were searched and sampled between Janu
PMID 24113221

Japanese Journal

ミトコンドリア遺伝子異常と内耳障害

山岨達也
耳鼻咽喉科臨床 104(8), 533-540, 2011-08-01
… Mitochondrial DNA lesions are closely associated with sensorineural hearing loss in approximately 70% of the three most common mitochondrial disorders: MELAS, MERRF, and CPEO. …
NAID 10029260261

L-arginine is effective in stroke-like episodes of MELAS associated with the G13513A mutation

SHIGEMI Ritsuko,FUKUDA Mitsumasa,SUZUKI Yuka,MORIMOTO Takehiko,ISHII Eiichi
Brain & development 33(6), 518-520, 2011-06-06
NAID 10029562181

Related Pictures

★リンクテーブル★

国試過去問	「102I074」「100A047」
リンク元	「ミトコンドリアミオパチー」「ミトコンドリア脳筋症」「ミトコンドリア脳筋症・乳酸アシドーシス・脳卒中様発作症候群」「脳卒中様発作」「mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes」
拡張検索	「MELAS症候群」

「102I074」

Mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke-like episodes
	Classification and external resources
	Basal ganglia calcification, cerebellar atrophy, increased lactate; a CT image of a person diagnosed with MELAS
ICD-10	G31.8
ICD-9	277.87
OMIM	540000
DiseasesDB	8254
eMedicine	ped/1406
MeSH	D017241

　　[★]

56歳の男性。歩行時のふらつきを主訴に4か月前に来院した。酒に酔っているかのように左右にふらふらして歩くようになり、本人は「平衡感覚がおかしい」、「視点を動かすと風景の残像がしばらく残る」、「夜になるとものが見にくい」、「字が読みにくい」などと訴えていた。食欲はあった。2か月前から喋らなくなり、意思の疎通が困難になり、一日布団の上で寝て過ごすようになった。妻が世話していたが、トイレには行かずにオムツを使っていた。今月から呼びかけに全く反応しなくなり、周囲の物に視線を向けなくなった。また体がカチカチになってきて、上半身を起こすことができなくなった。食べ物は口に押しつければ、なんとか食べることができた。るいそう、脱水、褥瘡、除皮質硬直、ミオクローヌス及び四肢深部腱反射亢進を認める。頭部単純MRIのT2強調像と拡散強調像とを以下に示す。
最も考えられるのはどれか。

[正答]

※国試ナビ4※　［102I073］←［国試_102］→［102I075］

「100A047」

　　[★]

4歳の女児。けいれん発作を主訴に来院した。3歳児健康診査で言葉の遅れを指摘された。4歳5か月時、保育所で昼寝中に意識障害と全身けいれんとを起こした。身長94.0cm(－2.5SD)、体重12.0㎏(－2.0SD)。体温36.8℃。呼吸数30/分。脈拍80/分、整。四肢と腰背部とに多毛がみられる。脳脊髄液所見：細胞数2/μl(基準0～2)、蛋白25mg/dl(基準15～45)、糖59mg/dl(基準50～75)。血清生化学所見：血糖130mg/dl、アンモニア40μg/dl(基準18～48)、乳酸82mg/dl(基準5～20)、ピルビン酸4.0mg/dl(基準0.3～0.9)。頭部単純MRIのT2強調像を以下に示す。
最も考えられるのはどれか。

[正答]

※国試ナビ4※　［100A046］←［国試_100］→［100A048］

「ミトコンドリアミオパチー」

　　[★]

英: mitochondrial myopathy
関: ミトコンドリア筋症、ミトコンドリアミオパシー

症状

筋力低下、何らかの中枢神経症状、低身長

主要疾患

1. 慢性進行性外眼筋麻痺症候群 CPEO カーンズ・セイヤー症候群 Kearns-Sayre症候群

症状：外眼筋麻痺
病因：mt DNAの欠失。遺伝性・先天性

2. myoclonus eplilepsy associated with ragged-red fibers MELAS メラス

小児期に発症
症状：突然起こる頭痛、嘔吐、痙攣、意識障害、片麻痺、半盲など。脳卒中様症状を繰り返し、次第に荒廃していく疾患
病因：mt DNAのtRNA Leuコード領域の点変異がほとんど。遺伝性。

3. mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes MERRF マーフ

症状：ミオクローヌスてんかん。小脳症状。
症状：知的退行
病因：mt DNAのtRNA Lysコード領域の点変異がほとんど。遺伝性

「ミトコンドリア脳筋症」

　　[★]

英: mitochondrial encephalomyopathy
関: ミトコンドリア筋症、ミトコンドリア心筋症

病因

ミトコンドリアDNAの変異

遺伝

母性遺伝

病型 (IMD,YN J154)

1. 慢性進行性外眼筋麻痺症候群 chronic progressive external opthalmoplegia CPEO=Kerns-Shy-Sayre KSS

外眼筋麻痺、四肢筋力低下、感音性難聴、網膜色素変性症、心伝導障害

2. mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes MELAS

周期性頭痛、嘔吐、けいれん発作、脳卒中様発作、感音性難聴、糖尿病

3. myoclonus epilepsy　associated with ragged-red fibers MERRF

ミオクローヌスてんかん、小脳失調

共通症状(YN.J154)

四肢の筋力低下、低身長、感音性難聴、知能低下、糖尿病

国試

104I058

「ミトコンドリア脳筋症・乳酸アシドーシス・脳卒中様発作症候群」

　　[★]

英: mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike episodes, mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike episodes, mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes, MELAS

「脳卒中様発作」

　　[★]

英: encephalopathy| lactic acidosis| and strokelike episodes
同: MELAS

「mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes」

　　[★] ミトコンドリア脳筋症・乳酸アシドーシス・脳卒中様発作症候群 MELAS

「MELAS症候群」

　　[★]

英: MELAS syndrome、mitochondrial myopathy、encephalopathy、lactic acidosis and stroke-like episode syndrome
関: ミトコンドリア脳筋症・乳酸アシドーシス・脳卒中様症候群

[1] Pavlakis SG, Phillips PC, DiMauro S, De Vivo DC, Rowland LP (1984). "Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes: a distinctive clinical syndrome". Ann Neurol 16 (4): 481–8. doi:10.1002/ana.410160409. PMID 6093682.

[2] Hirano M, Pavlakis SG (1994). "Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS): current concepts". J Child Neurol 9 (1): 4–13. doi:10.1177/088307389400900102. PMID 8151079.

[3] MELAS syndrome at NLM Genetics Home Reference

[4] Hirano M, Ricci E, Koenigsberger MR, Defendini R, Pavlakis SG, DeVivo DC, DiMauro S, Rowland LP (1992). "Melas: an original case and clinical criteria for diagnosis". Neuromuscul Disord 2 (2): 125–35. doi:10.1016/0960-8966(92)90045-8. PMID 1422200.

[pmid19946553-5] Abu-Amero KK, Al-Dhalaan H, Bohlega S, Hellani A, Taylor RW (2009). "A patient with typical clinical features of mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) but without an obvious genetic cause: a case report". J Med Case Reports 3: 77. doi:10.1186/1752-1947-3-77. PMC 2783076. PMID 19946553.

[pmid17080429-6] Rodriguez MC, MacDonald JR, Mahoney DJ, Parise G, Beal MF, Tarnopolsky MA (2007). "Beneficial effects of creatine, CoQ10, and lipoic acid in mitochondrial disorders". Muscle Nerve 35 (2): 235–42. doi:10.1002/mus.20688. PMID 17080429.

[pmid9003864-7] Ogle RF, Christodoulou J, Fagan E, et al. (1997). "Mitochondrial myopathy with tRNA(Leu(UUR)) mutation and complex I deficiency responsive to riboflavin". J. Pediatr. 130 (1): 138–45. doi:10.1016/S0022-3476(97)70323-8. PMID 9003864.

[pmid17276739-8] Koga Y, Akita Y, Nishioka J, et al. (2007). "MELAS and L-arginine therapy". Mitochondrion 7 (1-2): 133–9. doi:10.1016/j.mito.2006.11.006. PMID 17276739.

[pmid17889473-9] Hirata K, Akita Y, Povalko N, et al. (2007). "Effect of l-arginine on synaptosomal mitochondrial function". Brain Dev 30 (4): 238. doi:10.1016/j.braindev.2007.08.007. PMID 17889473.

Mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke-like episodes
Classification and external resources
Basal ganglia calcification, cerebellar atrophy, increased lactate; a CT image of a person diagnosed with MELAS
ICD-10	G31.8
ICD-9	277.87
OMIM	540000
DiseasesDB	8254
eMedicine	ped/1406
MeSH	D017241

匿名

検索

案内

MELAS