WordNet

make a map of; show or establish the features of details of; "map the surface of Venus"
to establish a mapping (of mathematical elements or sets) (同)represent
a diagrammatic representation of the earths surface (or part of it)
plan, delineate, or arrange in detail; "map ones future" (同)map out
depict as if on a map; "sorrow was mapped on the mothers face"
explore or survey for the purpose of making a map; "We havent even begun to map the many galaxies that we know exist"
locate within a specific region of a chromosome in relation to known DNA or gene sequences; "map the genes"
an impairment of health or a condition of abnormal functioning
any of numerous trees or shrubs of the genus Acer bearing winged seeds in pairs; north temperate zone
wood of any of various maple trees; especially the hard close-grained wood of the sugar maple; used especially for furniture and flooring
caused by or altered by or manifesting disease or pathology; "diseased tonsils"; "a morbid growth"; "pathologic tissue"; "pathological bodily processes" (同)morbid, pathologic, pathological
a thick sweet sticky liquid (同)sirup

PrepTutorEJDIC

(1枚1枚の)『地図』;天体図 / …‘の'地図を作る;…‘を'地図にかく
(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
『カエデ』,『モミジ』;〈U〉カエデ材(堅くて木目が美しく,家具用)
病気にかかった / 病的な,不健全な(morbid)
シロップ(砂糖や果汁を煮詰めて作る甘い汁) / (薬用の)シロップ剤

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/06/09 19:34:30」(JST)

wiki en

Maple syrup urine disease (MSUD), also called branched-chain ketoaciduria, is an autosomal recessive^[1] metabolic disorder affecting branched-chain amino acids. It is one type of organic acidemia.^[2] The condition gets its name from the distinctive sweet odor of affected infants' urine.^[3]

Causes

MSUD is a metabolic disorder caused by a deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), leading to a buildup of the branched-chain amino acids (leucine, isoleucine, and valine) and their toxic by-products (ketoacids) in the blood and urine. The enzyme complex consists of four subunits designated E₁α, E₁β, E₂, and E₃. The E₃ subunit is also a component of pyruvate dehydrogenase complex and oxoglutarate dehydrogenase complex.^[4] MSUD can result from mutations in any of the genes that code for the enzyme subunits.

Diagnosis and symptoms

The disease is named for the presence of sweet-smelling urine, with an odor similar to that of maple syrup. The smell is also present and sometimes stronger in the ear wax of an affected individual. Prior to the easy availability of plasma amino acid measurement, diagnosis was commonly made based on suggestive symptoms and odor. Affected individuals are now often identified with characteristic elevations on plasma amino acids who do not have the characteristic odor.^[5] The compound responsible for the odor is sotolon (sometimes spelled sotolone).^[6] Infants with this disease seem healthy at birth but if left untreated suffer severe brain damage and eventually die.

From early infancy, symptoms of the condition include poor feeding, vomiting, dehydration, lethargy, hypotonia, seizures, hypoglycaemia, ketoacidosis, opisthotonus, pancreatitis, coma and neurological decline.

Classification

Maple syrup urine disease can be classified by its pattern of signs and symptoms, or by its genetic cause. The most common and severe form of the disease is the classic type, which appears soon after birth. Variant forms of the disorder may appear later in infancy or childhood and are typically less severe, but still involve mental and physical problems if left untreated.

There are several variations of the disease:

Classic Severe MSUD
Intermediate MSUD
Intermittent MSUD
Thiamine-responsive MSUD
E3-Deficient MSUD with Lactic Acidosis

Management

Keeping MSUD under control requires careful monitoring of blood chemistry and involves both a special diet and frequent testing.

A diet with minimal levels of the amino acids leucine, isoleucine, and valine must be maintained in order to prevent neurological damage. As these three amino acids are required for proper metabolic function in all humans, specialized protein preparations containing substitutes and adjusted levels of the amino acids have been synthesized and tested, allowing MSUD patients to meet normal nutritional requirements without causing harm.^[7] Some patients with MSUD may also improve with administration of high doses of thiamine, a cofactor of the enzyme that causes the condition.

Usually, patients are also monitored by a dietitian. Their diet must be adhered to strictly and permanently. However, with proper management, those afflicted are able to live healthy, normal lives and not suffer the severe neurological damage associated with the disease.

Genetic prevalence

Maple syrup urine disease has an autosomal recessive pattern of inheritance.

Maple syrup urine disease affects approximately 1 out of 180,000 infants.^[8] Due in part to the founder effect,^[9] however, MSUD has a much higher prevalence in children of Amish, Mennonite, and Jewish descent.^[10]^[8]^[11]

Mutations in the following genes cause maple syrup urine disease:

BCKDHA (Online 'Mendelian Inheritance in Man' (OMIM) 608348)
BCKDHB (Online 'Mendelian Inheritance in Man' (OMIM) 248611)
DBT (Online 'Mendelian Inheritance in Man' (OMIM) 248610)
DLD (Online 'Mendelian Inheritance in Man' (OMIM) 238331)

These four genes produce proteins that work together as the branched-chain alpha-keto acid dehydrogenase complex. The complex is essential for breaking down the amino acids leucine, isoleucine, and valine, which are present in many kinds of food (in particular, protein-rich foods such as milk, meat, and eggs). Mutations in any of these genes reduce or eliminate the function of the enzyme complex, preventing the normal breakdown of isoleucine, leucine, and valine. As a result, these amino acids and their by-products build up in the body. Because high levels of these substances are toxic to the brain and other organs, this accumulation leads to the serious medical problems associated with maple syrup urine disease.

This condition has an autosomal recessive inheritance pattern, which means the defective gene is located on an autosome, and two copies of the gene - one from each parent - must be inherited to be affected by the disorder. The parents of a child with an autosomal recessive disorder are carriers of one copy of the defective gene, but are usually not affected by the disorder.

Screening

On 9 May 2014, the UK National Screening Committee (UK NSC) announced its recommendation to screen every newborn baby in the UK for four futher genetic disorders as part of its NHS Newborn Blood Spot Screening programme, including Maple syrup urine disease.^[12]

References

^ Podebrad F, Heil M, Reichert S, Mosandl A, Sewell AC, Böhles H (April 1999). "4,5-dimethyl-3-hydroxy-25H-furanone (sotolone)--the odour of maple syrup urine disease". Journal of Inherited Metabolic Disease 22 (2): 107–114. doi:10.1023/A:1005433516026. PMID 10234605.
^ Ogier de Baulny H, Saudubray JM (2002). "Branched-chain organic acidurias". Semin Neonatol. 7 (1): 65–74. doi:10.1053/siny.2001.0087. PMID 12069539.
^ [1]
Genetics Home Reference (GRH) - Genetic Conditions - Maple Syrup Urine Disease. GHR is a service of the U.S. National Library of Medicine. Reviewed February 2006; Published June 12, 2009
^ Pasquali, Marzia; Longo, Nicola (December 13, 2011). "58. Newborn screening and inborn errors of metabolism". In Burtis, Carl A.; Ashwood, Edward R.; Bruns, David E. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics (5th ed.). Elsevier Health Sciences. p. 2062. ISBN 978-1-4160-6164-9.
^ "#248600 Maple Syrup Urine Disease; MSUD". Johns Hopkins University. Retrieved 2012-11-04.
^ Strauss, Kevin A; Puffenberger, Erik G; Morton, D Holmes (January 30, 2006). "Maple Syrup Urine Disease". In Pagon, Roberta A; Bird, Thomas D; Dolan, Cynthia R; Stephens, Karen; Adam, Margaret P. GeneReviews™ [Internet]. University of Washington, Seattle (published December 15, 2009). PMID 20301495. Retrieved May 15, 2012{{inconsistent citations}}
^ Hallam P, Lilburn M, Lee PJ (2005). "A new protein substitute for adolescents and adults with maple syrup urine disease (MSUD)". J. Inherit. Metab. Dis. 28 (5): 665–672. doi:10.1007/s10545-005-0061-6. PMID 16151896.
^ ^a ^b http://rarediseases.about.com/od/rarediseases1/a/062004.htm
About.com: Rare diseases - June 2004. Maple syrup urine disease by Mary Kugler, R.N.
Article describes MSUD prevalence among Amish and Mennonite children.
^ Jaworski MA, Severini A, Mansour G, Konrad HM, Slater J, Henning K, Schlaut J, Yoon JW, Pak CY, Maclaren N, et al. (1989). "Genetic conditions among Canadian Mennonites: evidence for a founder effect among the old country (Chortitza) Mennonites". Clin Invest Med 12 (2): 127–141. PMID 2706837.
^ Puffenberger EG (2003). "Genetic heritage of Old Order Mennonites in southeastern Pennsylvania". Am J Med Genet C Semin Med Genet 121 (1): 18–31. doi:10.1002/ajmg.c.20003. PMID 12888983.
^ http://www.mazornet.com/genetics/MapleSyrup.htm
^ http://newbornbloodspot.screening.nhs.uk/news.php?id=12456

External links

Maple syrup urine disease at NLM Genetics Home Reference
Maple syrup urine disease at GPnotebook
msud at NIH/UW GeneTests
Maple Syrup Urine Disease (Overview on NLM)
Maple syrup urine disease at DMOZ

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. メープルシロップ尿症の概要 overview of maple syrup urine disease
2. 先天性代謝異常：代謝性救急疾患 inborn errors of metabolism metabolic emergencies
3. 先天性代謝異常：分類 inborn errors of metabolism classification
4. 幼児および小児における低血糖症の病因 etiology of hypoglycemia in infants and children
5. 新生児スクリーニング newborn screening

English Journal

Two novel compound heterozygous mutations in the BCKDHB gene that cause the intermittent form of maple syrup urine disease.

Guo Y1, Liming L2, Jiang L3,4.
Metabolic brain disease.Metab Brain Dis.2015 Dec;30(6):1395-400. doi: 10.1007/s11011-015-9711-z. Epub 2015 Aug 4.
Intermittent maple syrup urine disease (MSUD) is a potentially life-threatening metabolic disorder caused by a deficiency of branched chain α-ketoacid dehydrogenase (BCKD) complex. In contrast to classic MSUD, children with the intermittent form usually have an atypical clinical manifestation. Here
PMID 26239723

Intracerebroventricular administration of α-ketoisocaproic acid decreases brain-derived neurotrophic factor and nerve growth factor levels in brain of young rats.

Wisniewski MS1,2, Carvalho-Silva M1,2, Gomes LM1,2, Zapelini HG3, Schuck PF3, Ferreira GC4, Scaini G1,2, Streck EL5,6.
Metabolic brain disease.Metab Brain Dis.2015 Nov 20. [Epub ahead of print]
Maple syrup urine disease (MSUD) is an inherited aminoacidopathy resulting from dysfunction of the branched-chain keto acid dehydrogenase complex, leading to accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine and valine as well as their corresponding transaminated branched-cha
PMID 26586008

Direct tandem mass spectrometric analysis of amino acids in plasma using fluorous derivatization and monolithic solid-phase purification.

Tamashima E1, Hayama T1, Yoshida H1, Imakyure O1, Yamaguchi M1, Nohta H2.
Journal of pharmaceutical and biomedical analysis.J Pharm Biomed Anal.2015 Nov 10;115:201-7. doi: 10.1016/j.jpba.2015.07.008. Epub 2015 Jul 17.
In this study, we developed a novel direct tandem mass spectrometric method for rapid and accurate analysis of amino acids utilizing a fluorous derivatization and purification technique. Amino acids were perfluoroalkylated with 2H,2H,3H,3H-perfluoroundecan-1-al in the presence of 2-picoline borane v
PMID 26222276

Japanese Journal

小児肝臓移植の現状と展望

移植 50(6), 589-594, 2015
NAID 130005114876

愛媛県における新生児マス・スクリーニング

愛媛県立衛生環境研究所年報 (12), 8-13, 2009
NAID 40018854593

PCRを応用したメープルシロップ尿症の出生早期診断

Pediatrics international : official journal of the Japan Pediatric Society 50(3), 312-314, 2008-06-01
NAID 10025343574

Related Pictures

★リンクテーブル★

リンク元	「メープルシロップ尿症」「ビタミンB1」「アミノ酸代謝異常症」「branched-chain α-ketoacid dehydrogenase deficiency」
関連記事	「disease」「map」「maple」「syrup」

「メープルシロップ尿症」

Maple syrup urine disease
	Classification and external resources
	Isoleucine (pictured above), leucine, and valine are the branched-chain amino acids that build up in MSUD.
ICD-10	E71.0
ICD-9	270.3
OMIM	248600
DiseasesDB	7820
MedlinePlus	000373
MeSH	D008375

　　[★]

英: maple syrup urine disease MSUD
同: カエデシロップ尿症、楓糖尿症、分岐鎖ケト酸尿症分枝鎖ケト酸尿症 branched-chain ketoaciduria
関: 新生児マススクリーニング、分岐鎖アミノ酸、アミノ酸代謝異常症; 代謝異常による疾患.xls

概念

分岐鎖アミノ酸のα-ケト酸を脱炭酸する酵素の障害が原因となって生じるアミノ代謝異常症
新生児マススクリーニングの中では最も頻度が低い疾患

病因

分岐鎖α-ケト酸脱水素酵素(分枝α-ケト酸デヒドロゲナーゼ, BCKDH)の機能欠損により生じる。

R1R2CH-CO-COOH + NAD+ + CoASH → NADH + CO2 + R1R2CH-CO-SCoA

2-オキソ-3-メチル吉草酸(α-ケトメチルバレリン酸)　×→　2-メチルブチリルCoA　(イソロイシン)

2-オキソイソ吉草酸(α-ケトイソバレリン酸)　×→　イソブチリルCoA　(バリン)

2-オキソイソカプロン吉草酸(α-ケトイソカプロイン酸)　×→　イソバレリルCoA　(ロイシン)

疫学

日本での頻度は約60万人に1人

遺伝形式

常染色体性劣性遺伝

症状

痙攣、意識障害、昏睡、知能障害

生後3-5日より哺乳困難、吐乳、無呼吸発作、嗜眠、痙攣、痙性麻痺、後弓反張などの錐体路症状。
精神身体発達は障害される。

身体所見

汗：メープルシロップ様の臭い
尿：メープルシロップ様の特有の尿臭(分岐鎖アミノ酸とそのα-ケト酸)が含まれる

検査

新生児マススクリーニングにおいてガスリー法を用い行う。検出する物質はロイシン
血液検査：イソロイシン、ロイシン、バリン↑
尿検査：イソロイシン、ロイシン、バリン↑

診断

治療

急性期治療
食事療法(分枝鎖アミノ酸制限)

予後

予防

生後早期に発見し、低イソロイシン、ロイシン、バリン食を与える。

「ビタミンB1」

　　[★]

英: vitamine B1
同: チアミン thiamine、塩酸チアミン thiamine hydrochloride、ビタミンB1塩酸塩、アノイリン aneurine
商: アミグランド、パレセーフ、ビーフリード
関: ビタミン、チアミン二リン酸 thiamine pyrophosphate チアミンピロリン酸 TPP

水溶性ビタミン

機能

補酵素

体内でリン酸化されてピロリン酸エステルであるチアミン二リン酸(TPP)となり機能する。
α-ケト酸の酸化的脱炭酸反応(oxidative decarboxylation)、ケトール形成反応に関わる。
1. 解糖系からTCA回路を繋ぐ反応：チアミン二リン酸はピルビン酸デヒドロゲナーゼに非共有結合して、以下の脱炭酸反応を触媒

ピルビン酸 + CoASH + NAD⁺　－(ピルビン酸デヒドロゲナーゼ)→　アセチルCoA + NADH + CO₂

2. TCA回路の反応

α-ケトグルタル酸 + CoASH + NAD⁺ －(α-keto glutarate dehydrogenase)→　サクシニルCoA + NADH + CO₂

3. branched-chain ketoacid dehyrogenase: involved in metabolism of branched-chain amino acid; deficiency results in maple syrup urine disease

4. transketolase; hexose monophosphate shunt

5. 酵母などではアルコール発酵を行うピルビン酸デカルボキシラーゼ(ピルビン酸からCO₂を除去してアセトアルデヒドを産生)の補酵素として重要

ピルビン酸－(ピルビン酸デカルボキシラーゼ)→アセトアルデヒド + CO₂

臨床関連

ビタミンB₁欠乏症

「アミノ酸代謝異常症」

　　[★]

英: aminoacidopathy, disorder of aminoacid metabolism disorders of amino acid metabolism
同: アミノ酸代謝異常、先天性アミノ酸代謝異常症先天性アミノ酸代謝異常 inborn error of amino acid metabolism

[show details]

アミノ酸代謝異常 : 約 16,700 件
アミノ酸代謝異常症 : 約 76,400 件

アミノ酸代謝異常症

国試で出たことが有るレベル

アミノ酸代謝異常で痙攣を呈さないもの

チロシン血症、アルカプトン尿症、ヒスチジン血症

「branched-chain α-ketoacid dehydrogenase deficiency」

　　[★]

関: メープルシロップ尿症 maple syrup urine disease MSUD、分枝鎖αケト酸脱水素酵素

「disease」

　　[★]

n.

疾患：illnessより厳密な概念。「ある臓器に明確な障害が確認され、それによって症状が出ているとはっきり説明できる場合」 (PSY.9)

特定の原因、病態生理、症状、経過、予後、病理組織所見が全てそろった場合 (PSY.9)

something that is very wrong with people's attitudes, way of life or with society.

関: ail、ailment、disease entity、disorder、ill、illness、malady、sick、sickness

注意

disease ≠ illness ≠ disorder

「map」

　　[★]

n.

地図、マップ

v.

地図で表す、(遺伝子などを)位置づける、(遺伝子などが)位置する

関: lie、locate、location、loci、locus、mapping、position、rank、sit、situated、situation、stand、topo

「maple」

　　[★]

カエデ

関: Acer、Aceraceae

「syrup」

　　[★]

シロップ、糖蜜

関: molasses

[1] Podebrad F, Heil M, Reichert S, Mosandl A, Sewell AC, Böhles H (April 1999). "4,5-dimethyl-3-hydroxy-25H-furanone (sotolone)--the odour of maple syrup urine disease". Journal of Inherited Metabolic Disease 22 (2): 107–114. doi:10.1023/A:1005433516026. PMID 10234605.

[2] Ogier de Baulny H, Saudubray JM (2002). "Branched-chain organic acidurias". Semin Neonatol. 7 (1): 65–74. doi:10.1053/siny.2001.0087. PMID 12069539.

[3] [1]
Genetics Home Reference (GRH) - Genetic Conditions - Maple Syrup Urine Disease. GHR is a service of the U.S. National Library of Medicine. Reviewed February 2006; Published June 12, 2009

[Tietz2011-4] Pasquali, Marzia; Longo, Nicola (December 13, 2011). "58. Newborn screening and inborn errors of metabolism". In Burtis, Carl A.; Ashwood, Edward R.; Bruns, David E. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics (5th ed.). Elsevier Health Sciences. p. 2062. ISBN 978-1-4160-6164-9.

[omim-5] "#248600 Maple Syrup Urine Disease; MSUD". Johns Hopkins University. Retrieved 2012-11-04.

[GeneReviews-6] Strauss, Kevin A; Puffenberger, Erik G; Morton, D Holmes (January 30, 2006). "Maple Syrup Urine Disease". In Pagon, Roberta A; Bird, Thomas D; Dolan, Cynthia R; Stephens, Karen; Adam, Margaret P. GeneReviews™ [Internet]. University of Washington, Seattle (published December 15, 2009). PMID 20301495. Retrieved May 15, 2012{{inconsistent citations}}

[psynth-7] Hallam P, Lilburn M, Lee PJ (2005). "A new protein substitute for adolescents and adults with maple syrup urine disease (MSUD)". J. Inherit. Metab. Dis. 28 (5): 665–672. doi:10.1007/s10545-005-0061-6. PMID 16151896.

[msudam-8] ttp://rarediseases.about.com/od/rarediseases1/a/062004.htm
About.com: Rare diseases - June 2004. Maple syrup urine disease by Mary Kugler, R.N.
Article describes MSUD prevalence among Amish and Mennonite children.

[fe-9] Jaworski MA, Severini A, Mansour G, Konrad HM, Slater J, Henning K, Schlaut J, Yoon JW, Pak CY, Maclaren N, et al. (1989). "Genetic conditions among Canadian Mennonites: evidence for a founder effect among the old country (Chortitza) Mennonites". Clin Invest Med 12 (2): 127–141. PMID 2706837.

[msudmp-10] Puffenberger EG (2003). "Genetic heritage of Old Order Mennonites in southeastern Pennsylvania". Am J Med Genet C Semin Med Genet 121 (1): 18–31. doi:10.1002/ajmg.c.20003. PMID 12888983.

[msudaj-11] ttp://www.mazornet.com/genetics/MapleSyrup.htm

[12] ttp://newbornbloodspot.screening.nhs.uk/news.php?id=12456

Maple syrup urine disease
Classification and external resources
Isoleucine (pictured above), leucine, and valine are the branched-chain amino acids that build up in MSUD.
ICD-10	E71.0
ICD-9	270.3
OMIM	248600
DiseasesDB	7820
MedlinePlus	000373
MeSH	D008375

匿名

検索

案内

maple syrup urine disease