short-chain acyl-CoA dehydrogenase deficiency

短鎖アシルCoA脱水素酵素欠損症

WordNet

1. without possessing something at the time it is contractually sold; "he made his fortune by selling short just before the crash"
2. the location on a baseball field where the shortstop is stationed
3. low in stature; not tall; "he was short and stocky"; "short in stature"; "a short smokestack"; "a little man" (同)little
4. lacking foresight or scope; "a short view of the problem"; "shortsighted policies"; "shortsighted critics derided the plan"; "myopic thinking" (同)shortsighted, unforesightful, myopic
5. at a disadvantage; "I was caught short" (同)unawares
6. (primarily spatial sense) having little length or lacking in length; "short skirts"; "short hair"; "the board was a foot short"; "a short toss"
7. at some point or distance before a goal is reached; "he fell short of our expectations"
8. clean across; "the cars axle snapped short"
9. not holding securities or commodities that one sells in expectation of a fall in prices; "a short sale"; "short in cotton"
10. of speech sounds or syllables of relatively short duration; "the English vowel sounds in `pat, `pet, `pit, `pot, putt are short"
11. primarily temporal sense; indicating or being or seeming to be limited in duration; "a short life"; "a short flight"; "a short holiday"; "a short story"; "only a few short months"
12. so as to interrupt; "She took him up short before he could continue"
13. tending to crumble or break into flakes due to a large amount of shortening; "shortbread is a short crumbly cookie"; "a short flaky pie crust"
14. fasten or secure with chains; "Chain the chairs together"
15. a unit of length
16. a necklace made by a stringing objects together; "a string of beads"; "a strand of pearls"; (同)string, strand
17. a linked or connected series of objects; "a chain of daisies"
18. a series of (usually metal) rings or links fitted into one another to make a flexible ligament
19. anything that acts as a restraint
20. (chemistry) a series of linked atoms (generally in an organic molecule) (同)chemical chain
21. a series of things depending on each other as if linked together; "the chain of command"; "a complicated concatenation of circumstances" (同)concatenation
22. (business) a number of similar establishments (stores or restaurants or banks or hotels or theaters) under one ownership
23. connect or arrange into a chain by linking
24. the 3rd letter of the Roman alphabet (同)c
25. (music) the keynote of the scale of C major
26. a general-purpose programing language closely associated with the UNIX operating system
27. British biochemist (born in Germany) who isolated and purified penicillin, which had been discovered in 1928 by Sir Alexander Fleming (1906-1979) (同)Ernst Boris Chain, Sir Ernst Boris Chain

PrepTutorEJDIC

1. (長さ・時間・距離などが)『短い』,近い・(人が)『背が低い』・(数量・期間などが)不足の』,乏しい;目標(標準)に達しない・(文などが)『簡潔な』,手短な・『そっけない』,ぞんぞいな,無愛想な・(ケーキなどが)かりかりする,さくさくする・(母音・音節が)短い;(詩の行の母音が)強勢のない・急に,突然・短いもの;欠けているもの・短篇映画(short movie, short subject) ・=short circuit・《複数形で》不足,欠損 / …‘を'短絡させる,ショートさせる / 短絡する,ショートする
2. 『鎖』;(装飾用の)鎖 / 《複数形で》『束縛』,拘束;囚人をつなぐ鎖 / (物事の)『連続』,つながり《+『of』+『名』》 / (商店・銀行・ホテルなどの)チェーン(一連の店が同一資本のもとで連携して経営される方式;その店) / チェーン(測量で用いられる単位;約21.7m) / …'を'『鎖でつなぐ』《+『up』(『together』)+『名,』+『名』+『up』(『together』)》
3. 〈U〉〈C〉(…の)(量・額などの)不足,欠乏《+『of』(『in』)+『名』》 / 〈C〉不足分,不足量,不足額 / 〈C〉(精神・肉体などの)欠陥
4. carbonの化学記号

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/09/07 12:20:27」(JST)

wiki en

[Wiki en表示]

Short-chain acyl-coenzyme A dehydrogenase deficiency
Classification and external resources
ICD-9-CM	277.85
OMIM	201470
DiseasesDB	31599

Short-chain acyl-coenzyme A dehydrogenase deficiency (SCADD), also called ACADS deficiency and SCAD deficiency, is an autosomal recessive fatty acid oxidation disorder which affects enzymes required to break down a certain group of fats called short chain fatty acids.

Characteristics

Some affected infants will exhibit vomiting, low blood sugar (hypoglycemia), a lack of energy (lethargy), poor feeding, and failure to gain weight and grow at the expected rate (failure to thrive). Other features of this disorder may include poor muscle tone (hypotonia), seizures, developmental delays, and a small head size (microcephaly). The symptoms of short-chain acyl-CoA dehydrogenase deficiency may be triggered by periods of fasting or during illnesses such as viral infections. In some cases, signs and symptoms may not appear until adulthood, when some individuals may develop muscle weakness and wasting. Other people with gene mutations that can cause this disorder may have such mild symptoms that they are never diagnosed. Many biochemical geneticists consider this to be a biochemical phenotype with a very mild clinical phenotype or no clinical phenotype.

Cause and Genetics

Short-chain acyl-coenzyme A dehydrogenase deficiency has an autosomal recessive pattern of inheritance.

SCADD is caused by mutations in the ACADS gene, located on chromosome 12q22-qter. Mutations in the ACADS gene lead to inadequate levels of an enzyme called short-chain acyl-CoA dehydrogenase, which is important for the breakdown of short-chain fatty acids. Reduced levels of this enzyme prevent short-chain fatty acids from being further broken down and processed in the mitochondria (the energy-producing centers inside cells). As a result, these short-chain fatty acids are not converted into energy, which can lead to the signs and symptoms of this disorder, such as lethargy and hypoglycemia.

The disorder is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder is located on an autosome (chromosome 12 is an autosome), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.

Epidemiology

This disorder is thought to affect approximately 1 in 50,000 newborns.

References

External links

• GeneReviews/NCBI/NIH/UW entry on Short-Chain Acyl-CoA Dehydrogenase Deficiency
• Short-chain acyl-coenzyme A dehydrogenase deficiency at NLM Genetics Home Reference
• ACADS gene
• Short-chain acyl-coenzyme A (CoA) dehydrogenase (SCAD) deficiency at NIH's Office of Rare Diseases
• "Short-Chain Acyl-CoA Dehydrogenase Deficiency (SCAD)". Save Babies Through Screening Foundation. 
• "Acyl CoA dehydrogenase, short chain, deficiency of". Orphanet. 
• "SCAD". Disease Information from NORD, National Organization for Rare Disorders, Inc. 
• Bok LA, Vreken P, Wijburg FA et al. (November 2003). "Short-chain Acyl-CoA dehydrogenase deficiency: studies in a large family adding to the complexity of the disorder". Pediatrics 112 (5): 1152–5. doi:10.1542/peds.112.5.1152. PMID 14595061. 

UpToDate Contents

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• 1. 脂質およびプリン代謝障害による代謝性ミオパチー metabolic myopathies caused by disorders of lipid and purine metabolism
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English Journal

• Complex changes in the liver mitochondrial proteome of short chain acyl-CoA dehydrogenase deficient mice.

• Wang W1, Mohsen AW2, Uechi G3, Schreiber E3, Balasubramani M3, Day B3, Michael Barmada M4, Vockley J5.Author information 1Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai, China; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, USA. Electronic address: wangwei@shchildren.com.cn.2Division of Medical Genetics, Children's Hospital of Pittsburgh, Pittsburgh, USA.3Genomics and Proteomics Core laboratories, University of Pittsburgh, Pittsburgh, USA.4Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, USA.5Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, USA; Division of Medical Genetics, Children's Hospital of Pittsburgh, Pittsburgh, USA; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, USA.AbstractShort-chain acyl-CoA dehydrogenase (SCAD) deficiency is an autosomal recessive inborn error of metabolism that leads to the impaired mitochondrial fatty acid β-oxidation of short chain fatty acids. It is heterogeneous in clinical presentation including asymptomatic in most patients identified by newborn screening. Multiple mutations have been identified in patients; however, neither clear genotype-phenotype relationships nor a good correlation between genotype and current biochemical markers for diagnosis has been identified. The definition and pathophysiology of this deficiency remain unclear. To better understand this disorder at a global level, quantitative alterations in the mitochondrial proteome in SCAD deficient mice were examined using a combined proteomics approach: two-dimensional gel difference electrophoresis (2DIGE) followed by protein identification with MALDI-TOF/TOF and iTRAQ labeling followed by nano-LC/MALDI-TOF/TOF. We found broad mitochondrial dysfunction in SCAD deficiency. Changes in the levels of multiple energy metabolism related proteins were identified indicating that a more complex mechanism for development of symptoms may exist. Affected pathways converge on disorders with neurologic symptoms, suggesting that even asymptomatic individuals with SCAD deficiency may be at risk to develop more severe disease. Our results also identified a pattern associated with hepatotoxicity implicated in mitochondrial dysfunction, fatty acid metabolism, decrease of depolarization of mitochondria and mitochondrial membranes, and swelling of mitochondria, demonstrating that SCAD deficiency relates more directly to mitochondrial dysfunction and alteration of fatty acid metabolism. We propose several candidate molecules that may serve as markers for recognition of clinical risk associated with this disorder.
• Molecular genetics and metabolism.Mol Genet Metab.2014 Mar 12. pii: S1096-7192(14)00086-9. doi: 10.1016/j.ymgme.2014.02.014. [Epub ahead of print]
• Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is an autosomal recessive inborn error of metabolism that leads to the impaired mitochondrial fatty acid β-oxidation of short chain fatty acids. It is heterogeneous in clinical presentation including asymptomatic in most patients identified by ne
• PMID 24685553

• Proteomic investigation of cultivated fibroblasts from patients with mitochondrial short-chain acyl-CoA dehydrogenase deficiency.

• Edhager AV1, Stenbroen V1, Nielsen NS1, Bross P1, Olsen RK1, Gregersen N1, Palmfeldt J2.Author information 1Research Unit for Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.2Research Unit for Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark. Electronic address: johan.palmfeldt@ki.au.dk.AbstractShort-chain acyl-CoA dehydrogenase (SCAD) deficiency is a rare inherited autosomal recessive disorder with not yet well established mechanisms of disease. In the present study, the mitochondrial proteome of five symptomatic patients homozygous for missense variations in the SCAD gene ACADS was investigated in an extensive large-scale proteomic study to map protein perturbations linked to the disease. Fibroblast cultures of patient cells homozygous for either c.319C>T/p.Arg107Cys (n=2) or c.1138C>T/p.Arg380Trp (n=3) in ACADS, and healthy controls (normal human dermal fibroblasts), were studied. The mitochondrial proteome derived from these cultures was analyzed by label free proteomics using high mass accuracy nanoliquid chromatography tandem mass spectrometry (nanoLC-MS/MS). More than 300 mitochondrial proteins were identified and quantified. Thirteen proteins had significant alteration in protein levels in patients carrying variation c.319C>T in ACADS compared to controls and they belonged to various pathways, such as the antioxidant system and amino acid metabolism. Twenty-two proteins were found significantly altered in patients carrying variation c.1138C>T which included proteins associated with fatty acid β-oxidation, amino acid metabolism and protein quality control system. Three proteins were found significantly regulated in both patient groups: adenylate kinase 4 (AK4), nucleoside diphosphate kinase A (NME1) and aldehyde dehydrogenase family 4 member A1 (ALDH4A1). Proteins AK4 and NME1 deserve further investigation because of their involvement in energy reprogramming, cell survival and proliferation with relevance for SCAD deficiency and related metabolic disorders.
• Molecular genetics and metabolism.Mol Genet Metab.2014 Mar;111(3):360-8. doi: 10.1016/j.ymgme.2014.01.007. Epub 2014 Jan 24.
• Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is a rare inherited autosomal recessive disorder with not yet well established mechanisms of disease. In the present study, the mitochondrial proteome of five symptomatic patients homozygous for missense variations in the SCAD gene ACADS was inves
• PMID 24485985

• Ethylmalonic Acid Induces Permeability Transition in Isolated Brain Mitochondria.

• Cecatto C1, Amaral AU, Leipnitz G, Castilho RF, Wajner M.Author information 1Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal de Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, 90035-003, Brazil.AbstractPredominant accumulation of ethylmalonic acid (EMA) in tissues and biological fluids is a characteristic of patients affected by short chain acyl-CoA dehydrogenase deficiency and ethylmalonic encephalopathy. Neurological abnormalities are frequently found in these disorders, but the mechanisms underlying the brain injury are still obscure. Since hyperlacticacidemia is also found in many affected patients indicating a mitochondrial dysfunction; in the present work, we evaluated the in vitro and ex vivo effects of EMA plus Ca2+ on mitochondrial integrity and redox balance in succinate-supported brain organelles. We verified that the evaluated parameters were disturbed only when EMA was associated with exogenous micromolar Ca2+ concentrations. Thus, we found that this short chain organic acid plus Ca2+ dissipated the membrane potential and provoked mitochondrial swelling, as well as impaired the mitochondrial Ca2+ retention capacity, resulting in a rapid Ca2+ release and decreased NAD(P)H matrix content. In contrast, EMA was not able to stimulate mitochondrial hydrogen peroxide generation. We also observed that all these effects were prevented by the mitochondrial Ca2+ uptake inhibitor ruthenium red and the mitochondrial permeability transition (MPT) inhibitors cyclosporin A (CsA) and ADP. Furthermore, mitochondria isolated from rat brains after in vivo intrastriatal administration of EMA was more susceptible to Ca2+-induced swelling, which was fully prevented by CsA and ADP. Finally, EMA significantly decreased striatal slice viability, which was attenuated by CsA. The data strongly indicate that EMA reduced the mitochondrial threshold for Ca2+-induced MPT reinforcing the role of this cation in EMA-induced disruption of mitochondrial bioenergetics. It is, therefore, presumed that EMA acting synergistically with Ca2+ compromises mitochondrial energy homeostasis in the central nervous system that may explain at least in part the neurologic alterations presented by patients with abnormal levels of this organic acid.
• Neurotoxicity research.Neurotox Res.2014 Feb 21. [Epub ahead of print]
• Predominant accumulation of ethylmalonic acid (EMA) in tissues and biological fluids is a characteristic of patients affected by short chain acyl-CoA dehydrogenase deficiency and ethylmalonic encephalopathy. Neurological abnormalities are frequently found in these disorders, but the mechanisms under
• PMID 24557940

Japanese Journal

• Role of common gene variations in the molecular pathogenesis of short- chain acyl-CoA dehydrogenase deficiency

• Pediatr Res 49, 18-23, 2001
• NAID 30027175610

Related Links

• Short-chain acyl-CoA dehydrogenase deficiency

Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is a condition that prevents the body from converting certain fats into energy, especially during periods without food (fasting). Signs and symptoms of SCAD ...

• Short-Chain Acyl-CoA Dehydrogenase Deficiency ...

Summary Disease characteristics. The clinical findings in those with confirmed short-chain acyl-coA dehydrogenase (SCAD) deficiency range from severe (dysmorphic facial features, feeding difficulties/failure to thrive, metabolic ...

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★リンクテーブル★

リンク元	「短鎖アシルCoA脱水素酵素欠損症」
関連記事	「deficiency」「short」「C」「chain」「CoA」

「短鎖アシルCoA脱水素酵素欠損症」

　　[★]

英

short-chain acyl-CoA dehydrogenase deficiency, SCADD

同？

短鎖アシルCoA脱水素酵素欠損症候群 deficiency of short-chainacyl-CoA dehydrogenase syndrome

関

短鎖アシルCoA脱水素酵素

[show details]

短鎖アシルCoA脱水素酵素欠損症 : 21 件
短鎖アシルCoA脱水素酵素欠損症候群 : 1 件

「deficiency」

　　[★]

• n.

• 不足、欠乏、欠失、欠如、欠損、不十分。栄養不足、栄養素欠乏、欠乏症。(遺伝子)(染色体内の)遺伝子欠失
• 欠けているもの、不足している物。不足分。不完全なもの、欠点のあるもの

関

absence, agenesis, dearth, defect, defective, deficient, deficit, delete, deletion, deletional, depletion, deprivation, deprive, lack, miss, missing, morphological defect, paucity, scarce, scarcity, starve

　

「short」

　　[★]

• adj.

• (比較級shorter-最上級shortest)短い、不足した、乏しい、省略された

関

abbreviated、brevis、brief、dearth、deficit、in short、insufficiency、insufficient、lack、paucity、poor、scant、scanty、scarce、scarcity、shortage、shortness

　 　 　 　 　 　 　 　 　 　 　 　 　 　

「C」

　　[★]

• 炭素 carbon
• シトシン cytosine
• システイン cysteine
• シチジン
• セルシウス度 摂氏 degrees Celsius degree C
• 産婦人科領域で「子宮外頚 子宮外頚部 exocervix」を表現するための略語

　 　 　 　

「chain」

　　[★]

• n.

• 鎖、チェーン

• adj.

• 鎖状の、鎖式の

関

open-chain、strand

　 　 　 　 　 　 　 　 　 　 　

「CoA」

　　[★]

• 大動脈縮窄症 coactation of the aorta
• 補酵素A coenzyme A