mitochondrial DNA depletion syndrome

ミトコンドリアDNA枯渇症候群 MDS

WordNet

1. the state of being depleted
2. the act of decreasing something markedly
3. a pattern of symptoms indicative of some disease
4. a complex of concurrent things; "every word has a syndrome of meanings"
5. the 4th letter of the Roman alphabet (同)d

PrepTutorEJDIC

1. 枯渇,消耗
2. (疾患の徴候となる一群の)症徴候,症候群 / (事件・社会的状態などのパターンを示す)徴候形態
3. deuteriumの化学記号
4. deoxyribonucleic acidディオキシリボ核酸

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/05/26 12:45:25」(JST)

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Mitochondrial DNA depletion syndrome (MDS) refers to a group of autosomal recessive disorders which cause the affected tissues to suffer from a significant drop in mitochondrial DNA. Symptoms may manifest as myopathic, hepatopathic, and/or encephalomyopathic. These syndromes affect tissue found in the muscle, liver, or both the muscle and brain, respectively. The condition is typically fatal in infancy and early childhood, though some have survived to their teenage years with the myopathic variant. There is currently no curative treatment for any form of MDSs, though some preliminary treatments have shown a reduction in symptoms.

Causes

The myopathic form of MDS manifests symptoms within the first year of life, and is diagnosed by higher levels of serum creatine kinase, which is atypical in other mitochondrial myopathies. Myopathic MDSs is strongly correlated to a variety of mutations in the gene TK2, seeing a reduction of TK2 activity to less than 32% in MDS patients found with the mutation. Because TK2 plays a key role in the mitochondrial salvage pathways of several deoxyribonucleoside triphosphates (dNTPs), a lowered activity would lead to less cycling of nucleotides. This lack of nucleotide recycling is detrimental since the mitochondria cannot synthesize entirely new deoxynucleotides, and the inner membrane of the mitochondria prevents the negatively charged nucleotides of the cytosol from entering.

The encephalomyopathic form of MDS is commonly characterized by psychomotor retardation, muscle hypotonia, hearing impairment, and generalized seizures. A common mutation in this form of MDSs involves a mutation in the SUCLA2 gene, which codes for the beta-subunit of SCS-A. This enzyme catalyzes the synthesis of succinate and coenzyme A into succinyl-CoA, but is also associated with the complex formed by nucleoside diphosphate kinase (NDPK) in the last step of the dNTP salvage pathway.

The hepatopathic form of MDS involves the onset of symptoms including hypotonia, hypoglycemia, persistent vomiting, and failure to thrive within the first year of life. Mutations in three genes have been linked to hepatopathic MDS: DGUOK, POLG, and MPV17. DGUOK encodes for mitochondrial deoxyguanosine kinase (dGK), which catalyzes the phosphorylation of deoxyribonucleosides into nucleotides. POLG encodes for the catalytic subunit pol γA, which is part of mitochondrial DNA polymerase.

References

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. 新生児胆汁うっ滞の原因 causes of neonatal cholestasis
• 3. 先天異常の遺伝学的および環境的原因 genetic and environmental causes of birth defects
• 4. 全身疾患と関連した遺伝性ニューロパチー hereditary neuropathies associated with generalized disorders
• 5. メンデル遺伝の概要 overview of mendelian inheritance

English Journal

• Polymerase gamma deficiency (POLG): Clinical course in a child with a two stage evolution from infantile myocerebrohepatopathy spectrum to an Alpers syndrome and neuropathological findings of Leigh's encephalopathy.

• Scalais E, Francois B, Schlesser P, Stevens R, Nuttin C, Martin JJ, Van Coster R, Seneca S, Roels F, Van Goethem G, Löfgren A, De Meirleir L.SourceDivision of Paediatric Neurology, Centre Hospitalier de Luxembourg, Luxembourg.
• European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society.Eur J Paediatr Neurol.2012 Sep;16(5):542-8. Epub 2012 Feb 17.
• AIMS: Description of the clinical course in a child compound heterozygous for POLG1 mutations, neuropathology findings and results of dietary treatment based on fasting avoidance and long chain triglycerides (LCT) restriction.RESULTS: At 3(1/2) months of age the patient presented with severe hypogly
• PMID 22342071

• In vitro supplementation with deoxynucleoside monophosphates rescues mitochondrial DNA depletion.

• Bulst S, Holinski-Feder E, Payne B, Abicht A, Krause S, Lochmüller H, Chinnery PF, Walter MC, Horvath R.SourceMedical Genetic Center, Munich, Germany; Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University of Munich, Germany.
• Molecular genetics and metabolism.Mol Genet Metab.2012 Sep;107(1-2):95-103. doi: 10.1016/j.ymgme.2012.04.022. Epub 2012 May 3.
• Mitochondrial DNA depletion syndromes are a genetically heterogeneous group of often severe diseases, characterized by reduced cellular mitochondrial DNA content. Investigation of potential therapeutic strategies for mitochondrial DNA depletion syndromes will be dependent on good model systems. We h
• PMID 22608879

Japanese Journal

• ミトコンドリア病(ミトコンドリア呼吸鎖異常症)--最も頻度の高い先天代謝異常症 (ミニ特集 先天代謝異常の診断と治療Update)

• 村山 圭,森 雅人,大竹 明
• 小児科臨床 63(10), 2071-2079, 2010-10
• NAID 40017279790

• Children's toxicology from bench to bed - Liver Injury (4) : Mitochondrial respiratory chain disorder and liver disease in children

• Murayama Kei,Ohtake Akira
• Journal of toxicological sciences 34(Special Issue II), SP237-SP243, 2009-07
• … Objectives: The present study was aimed to ascertain the contributions of mitochondrial respiratory chain (MRC) enzymes to the development of liver failure and to the liver pathophysiology of metabolic liver diseases. … They were diagnosed as mtDNA depletion syndrome. …
• NAID 110007337715

Related Links

• Mitochondrial DNA Depletion - Orphanet

The mtDNA depletion syndrome (MDS) is a clinically heterogeneous group of mitochondrial disorders characterized by a ... Mitochondrial DNA depletion syndrome; mitochondrial deoxythymidine kinase (TK2); mitochondrial deoxyguanosine ...

• Orphanet: Mitochondrial DNA depletion syndrome

The mitochondrial DNA (mtDNA) depletion syndrome (MDS) is a clinically heterogeneous group of mitochondrial disorders characterized by a reduction of the mtDNA copy number in affected tissues without mutations or rearrangements in the ...

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★リンクテーブル★

リンク元	「MDS」「ミトコンドリアDNA枯渇症候群」
関連記事	「D」「depletion」「DNA」「mitochondrial」「mitochondrial DNA」

「MDS」

　　[★]

• 骨髄異形成症候群 myelodysplastic syndrome
• ミラー・ディーカー症候群 Miller-Dieker syndrome
• ミトコンドリアDNA枯渇症候群 mitochondrial DNA depletion syndrome

「ミトコンドリアDNA枯渇症候群」

　　[★]

英

mitochondrial DNA depletion syndrome MDS

「D」

　　[★]

• アスパラギン酸
• ジヒドロウリジン
• 遠位の distal,
• うつ病 depression
• 下行結腸 descending colon(大腸内視鏡検査の結果を記載するときに用いる)

　 　

「depletion」

　　[★]

• n.

• 枯渇、欠乏

関

dearth、deficiency、deficient、deficit、deplete、deprivation、deprive、lack、paucity、scarce、scarcity、starve

　 　 　

「DNA」

　　[★]

英

deoxyribonucleic acid

同

デオキシリボ核酸

関

リボ核酸 RNA

　

「mitochondrial」

　　[★]

• adj.

• ミトコンドリアの

関

mitochondria、mitochondrially、mitochondrion

「mitochondrial DNA」

　　[★] ミトコンドリアDNA mtDNA