WordNet

complicated in structure; consisting of interconnected parts; "a complex set of variations based on a simple folk melody"; "a complex mass of diverse laws and customs"
a compound described in terms of the central atom to which other atoms are bound or coordinated (同)coordination_compound
a conceptual whole made up of complicated and related parts; "the complex of shopping malls, houses, and roads created a new town" (同)composite
(psychoanalysis) a combination of emotions and impulses that have been rejected from awareness but still influence a persons behavior
an impairment of health or a condition of abnormal functioning
caused by or altered by or manifesting disease or pathology; "diseased tonsils"; "a morbid growth"; "pathologic tissue"; "pathological bodily processes" (同)morbid, pathologic, pathological

PrepTutorEJDIC

『いくつかの部分から成る』,複合の,合成の / 『複雑な』,入りくんだ,こみいった(complicated) / 複合体,合成物 / コンプレックス,複合(抑圧されて心に残った複雑なしこり)
(体の)『病気』,疾患 / (精神・道徳などの)病気,病弊
女性の話術芸人 =diseur
〈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
病気にかかった / 病的な,不健全な(morbid)

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/11/06 09:39:44」(JST)

wiki en

Pyruvate Dehydrogenase Deficiency (PDH) is one of the most common neurodegenerative disorders associated with abnormal mitochondrial metabolism. ""PDH deficiency"" is an X-linked disease that shows heterogeneous characteristics in both clinical presentation and biochemical abnormality. The ""PDH Complex"" is a multi-enzyme complex that plays a vital role as a key regulatory step in the central pathways of energy metabolism in the mitochondria.

Inheritance and pathophysiology

The most commonly seen form of “”Pyruvate Dehydrogenase Complex Deficiency”” is caused by mutations in the X-linked E1 alpha gene and is approximately equally prevalent in both males and females. However, a greater severity of symptoms tends to affect males more often than heterozygous females. This can be explained by x-inactivation, as females carry one normal and one mutant gene. Cells with a normal allele active can metabolize the lactic acid that is released by the PDH deficient cells. They cannot, however, supply ATP to these cells and, therefore, phenotype depends largely on the nature/severity of the mutation.^[1]^[2]

Clinical Presentation

“”Pyruvate Dehydrogenase Complex Deficiency”” is generally present in one of two forms. The metabolic form appears as lactic acidosis and a blood lactate concentration of approximately >10 mmol/L. The neurological form of “”PDH deficiency”” contributes to hypotonic, poorly fed, lethargic and structurally abnormal in the brain patients who later may develop seizures and/or neuropathological spasms. These presentation of the disease usually progresses to mental retardation, microcephaly, blindness and spasticity.^[1]

Females with residual “”PDH”” activity will have no uncontrollable systemic lactic acidosis and few, if any, neurological symptoms. Conversely, females with little to no enzyme activity will have major structural brain abnormalities and atrophy. Males with mutations that abolish, or almost abolish, enzyme activity presumably die in utero because brain cells are not able to generate enough ATP to be functional viable. It is expected that most cases will be of mild severity and a clinical presentation involving lactic acidosis.^[2]

Prenatal onset may be presented with non-specific signs such as low Apgar scores and small for gestational age. Metabolic disturbances may also be considered with poor feeding and lethargy out of proportion to a mild viral illness, and especially after bacterial infection has been ruled out.^[1]

Treatment

Direct treatment that stimulates the pyruvate dehydrogenase complex (PDC), provides alternative fuels, and prevents acute worsening of the syndrome. However, some correction of acidosis does not reverse all the symptoms. CNS damage is common and limits a full recovery.

Ketogenic diets, with high fat and low carbohydrate intake have been used to control or minimize lactic acidosis but have shown marginal success.

There is some evidence that dichloroacetate reduces the inhibitory phosphorylation of pyruvate dehydrogenase complex and thereby activates any residual functioning complex. Resolution of lactic acidosis is observed in patients with E1 alpha enzyme subunit mutations that reduce enzyme stability. However, treatment with dichloroacetate does not improve neurological damage.^[1]

Oral citrate is often used to treat acidosis.

References

^ ^a ^b ^c ^d G K Brown, L J Otero, M LeGris, and R M Brown (November 1994). "Pyruvate dehydrogenase deficiency". J Med Genet. 31 (11): 875–879. doi:10.1136/jmg.31.11.875. PMC 1016663. PMID 7853374. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1016663/pdf/jmedgene00001-0059.pdf.
^ ^a ^b H H Dahl (March 1995). "Pyruvate dehydrogenase E1 alpha deficiency: males and females differ yet again.". Am J Hum Genet. 56 (3): 553–557. PMC 1801181. PMID 7887408. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1801181/pdf/ajhg00029-0006.pdf.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 遺伝性運動失調の概要 overview of the hereditary ataxias
2. 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
3. 水溶性ビタミンの概要 overview of water soluble vitamins
4. 消失性白質疾患（Vanishing white matter disease） vanishing white matter disease
5. 成人における小脳性運動失調の概要 overview of cerebellar ataxia in adults

English Journal

Possible therapeutic effects of myxobacterial metabolites on type I Gaucher disease.

Kim SJ, Kang S, Kim JB.SourceDepartment of Biotechnology, Hoseo University, 165 Baebang, Asan, Chungnam, Republic of Korea.
Gene.Gene.2012 Aug 10;504(2):156-9. Epub 2012 May 24.
Gaucher disease (GD) is the most prevalent lysosomal storage disorder caused by an inherited deficiency of glucocerebrosidase. In the present study, we aimed to determine whether myxobacterial metabolites exhibit a potential therapeutic effect in the cells from a patient with type I GD. We screened
PMID 22634098

The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients.

Patel KP, O'Brien TW, Subramony SH, Shuster J, Stacpoole PW.SourceDepartment of Medicine (Division of Endocrinology, Metabolism and Diabetes), College of Medicine, University of Florida, Gainesville, FL 32611, USA.
Molecular genetics and metabolism.Mol Genet Metab.2012 Jul;106(3):385-94.
CONTEXT: Pyruvate dehydrogenase complex (PDC) deficiency is a genetic mitochondrial disorder commonly associated with lactic acidosis, progressive neurological and neuromuscular degeneration and, usually, death during childhood. There has been no recent comprehensive analysis of the natural history
PMID 22896851

Japanese Journal

Thiamin and Alzheimers Disease

BLASS J. P.,SHEU K.-F. R.,COOPER A. J. L.,JUNG E. H.,GIBSON G. E.
Journal of Nutritional Science and Vitaminology 38(Special), 401-404, 1992
… Because of Clinical and neuropathological overlap between The Characteristics of dementia of The Alzheimer type (DAT) and of a Human thiamin deficiency syndrome (Wernicke-Korsakoff syndrome), Thiamin pyrophosphate (TPP) dependent processes have been studied in DAT brain and other tissues. …
NAID 130001369607

Related Pictures

★リンクテーブル★

リンク元	「ピルビン酸デヒドロゲナーゼ複合体欠損症」
関連記事	「disease」「deficiency」「complex」「complexed」「complexes」

「ピルビン酸デヒドロゲナーゼ複合体欠損症」

Pyruvate Dehydrogenase Complex Deficiency
	Classification and external resources
ICD-10	E74.4
ICD-9	271.8
OMIM	312170
DiseasesDB	30060
eMedicine	ped/1969
MeSH	D015325