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a blood disorder characterized by an increased concentration of hydrogen ions in the blood (which falls below 7 on the pH scale)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/02/13 14:07:34」(JST)

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Methylmalonic acidemia (MMA), also called methylmalonic aciduria, is an autosomal recessive^[1] metabolic disorder.^[2] It is a classical type of organic acidemia.^[3]

Methylmalonic acidemia stems from several genotypes,^[4] all forms of the disorder usually diagnosed in the early neonatal period, presenting progressive encephalopathy, and secondary hyperammonemia. The disorder can result in death if undiagnosed or left untreated.

Causes

Genetic

Methylmalonic acidemia has an autosomal recessive pattern of inheritance.

Methylmalonic acidemia is caused by a defect in the vitamin B₁₂-dependent enzyme methylmalonyl CoA mutase.

The inherited forms of methylmalonic acidemia cause defects in the metabolic pathway where methylmalonyl-coenzyme A (CoA) is converted into succinyl-CoA by the enzyme methylmalonyl-CoA mutase.^[5]

Vitamin B₁₂ is also needed for the conversion of methylmalonyl-CoA to Succinyl-CoA. Mutations leading to defects in vitamin B₁₂ metabolism or in its transport frequently result in the development of methylmalonic acidemia.

This disorder 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.

Nutritional

A severe nutritional deficiency of vitamin B₁₂ can also result in methylmalonic acidemia.^[6] Methylmalonyl CoA requires vitamin B₁₂ to form succinyl-CoA. When the amount of B₁₂ is insufficient for the conversion of cofactor methylmalonyl-CoA into succinyl-CoA, the buildup of unused methylmalonyl-CoA eventually leads to methylmalonic acidemia. This diagnosis is often used as an indicator of vitamin B₁₂ deficiency in serum.^[7]

Pathogenesis

Methylmalonic acidemia has varying diagnoses, treatment requirements and prognoses, which are determined by the specific genetic mutation causing the inherited form of the disorder.^[4] The following are the known genotypes responsible for methylmalonic acidemia:

OMIM	Name	Gene
251100	cblA type	MMAA
251110	cblB type	MMAB
277400	cblC type	MMACHC
277410	cblD type	MMADHC^[8]
277380	cblF type	LMBRD1^[9]
251000	mut type	MUT

References

^ Radmanesh, A; Zaman, T; Ghanaati, H; Molaei, S; Robertson, Rl; Zamani, Aa (July 2008). "Methylmalonic acidemia: brain imaging findings in 52 children and a review of the literature". Pediatric radiology 38 (10): 1054–61. doi:10.1007/s00247-008-0940-8. PMID 18636250.
^ http://www.genome.gov/19016901
^ Dionisi-Vici C, Deodato F, Raschinger W, Rhead W, Wilcken B (2006). "Classical organic acidurias, propionic aciduria, methylmalonic aciduria, and isovaleric aciduria: long-term outcome and effects of expanded newborn screening using tandem mass spectrometry". J Inherit Metab Dis. 29 (2-3): 383–389. doi:10.1007/s10545-006-0278-z. PMID 16763906.
^ ^a ^b Matsui, Sm; Mahoney, Mj; Rosenberg, Le (April 1983). "The natural history of the inherited methylmalonic acidemias" (Free full text). The New England Journal of Medicine 308 (15): 857–61. doi:10.1056/NEJM198304143081501. ISSN 0028-4793. PMID 6132336. http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+68-19-9.
^ Sakomoto O, Ohura T, Matsubara Y, Takayanagi M, Tsuchiya S (2007). "Mutation and haplotype analyses of the MUT gene in Japanese patients with methylmalonic acidemia". J Hum Genet. 52 (1): 48–55. doi:10.1007/s10038-006-0077-2. PMID 17075691.
^ Higginbottom MC, Sweetman L, Nyhan WL (1978). "A syndrome of methylmalonic aciduria, homocystinuria, megaloblastic anemia and neurological abnormalities in a vitamin B₁₂-deficient breast-fed infant of a strict vegetarian". N Engl J Med. 299 (7): 317–323. doi:10.1056/NEJM197808172990701. PMID 683264.
^ http://www.biology.arizona.edu/biochemistry/problem_sets/b12/04t.html
Vitamin B₁₂ deficiency - The methylmalonic aciduria connection
^ Gene identification for the cblD defect of vitamin B₁₂ metabolism. Coelho D, Suormala T, Stucki M, Lerner-Ellis JP, Rosenblatt DS, Newbold RF, Baumgartner MR, Fowler B. N Engl J Med. 2008 Apr 3;358(14):1454-64. PMID 18385497
^ Identification of a putative lysosomal cobalamin exporter altered in the cblF defect of vitamin B₁₂ metabolism. Rutsch F, Gailus S, Miousse IR, Suormala T, Sagné C, Toliat MR, Nürnberg G, Wittkampf T, Buers I, Sharifi A, Stucki M, Becker C, Baumgartner M, Robenek H, Marquardt T, Höhne W, Gasnier B, Rosenblatt DS, Fowler B, Nürnberg P. Nat Genet. 2009 Feb;41(2):234-9. Epub 2009 Jan 11. PMID 19136951

External links

Organic Acidemia Association
Methylmalonic acidemia at NLM Genetics Home Reference
Washington Health Center
GeneReviews article on Methylmalonic Acidemia
GeneReviews article on Disorders of Intracellular Cobalamin Metabolism
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UpToDate Contents

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1. 有機酸血症 organic acidemias
2. 先天性代謝異常：疫学、病因、および臨床的特徴 inborn errors of metabolism epidemiology pathogenesis and clinical features
3. 先天性代謝異常：分類 inborn errors of metabolism classification
4. 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
5. 先天性代謝異常：代謝性救急疾患 inborn errors of metabolism metabolic emergencies

English Journal

Assay for methylmalonyl coenzyme A mutase activity based on determination of succinyl coenzyme A by ultrahigh-performance liquid chromatography tandem mass spectrometry.

Gotoh K1, Nakajima Y, Tajima G, Hotta Y, Kataoka T, Kawade Y, Sugiyama N, Ito T, Kimura K, Maeda Y.
Analytical and bioanalytical chemistry.Anal Bioanal Chem.2015 Jul;407(18):5281-6. doi: 10.1007/s00216-015-8753-8. Epub 2015 May 28.
Methylmalonic acidemia (MMA) is an inherited metabolic disease. In this condition, metabolism from methylmalonyl coenzyme A (CoA) to succinyl-CoA is inhibited because of either low methylmalonyl-CoA mutase (MCM) activity or adenosylcobalamin deficiency owing to altered vitamin B12 metabolism. A high
PMID 26018627

Early Liver Transplantation for Neonatal-Onset Methylmalonic Acidemia.

Spada M1, Calvo PL1, Brunati A2, Peruzzi L3, Dell'Olio D4, Romagnoli R2, Porta F5.
Pediatrics.Pediatrics.2015 Jun 15. pii: peds.2015-0175. [Epub ahead of print]
With conventional dietary treatment, the clinical course of methylmalonic acidemia due to cobalamin-unresponsive methylmalonyl-CoA mutase (MCM) deficiency is characterized by the persistent risk of recurrent life-threatening decompensation episodes with metabolic acidosis, hyperammonemia, and coma.
PMID 26077484

Compartmentation of metabolism of the C12-, C9-, and C5-n-dicarboxylates in rat liver, investigated by mass isotopomer analysis: Anaplerosis from dodecanedioate.

Jin Z1, Bian F1, Tomcik K1, Kelleher JK2, Zhang GF3, Brunengraber H4.
The Journal of biological chemistry.J Biol Chem.2015 Jun 12. pii: jbc.M115.651737. [Epub ahead of print]
We investigated the compartmentation of the catabolism of dodecanedioate (DODA), azelate and glutarate in perfused rat livers, using a combination of metabolomics and mass isotopomer analyses. Livers were perfused with recirculating or nonrecirculating buffer containing one fully 13C-labeled dicarbo
PMID 26070565

Japanese Journal

Clinical features and management of organic acidemias in Japan

Fujisawa Daisuke,Nakamura Kimitoshi,Mitsubuchi Hiroshi [他]
Journal of human genetics 58(12), 769-774, 2013-12
NAID 40019919245

持続透析を行った新生児高アンモニア血症の3例

木原裕貴,福原里恵,藤原信,羽田聡,古川亮,佐藤友紀,西香代子
日本周産期・新生児医学会雑誌 = Journal of Japan Society of Perinatal and Neonatal Medicine 48(4), 981-985, 2012-12-15
NAID 10031154116

有機酸代謝異常症2例の成長経過における栄養管理の重要性についての検討

吉田彩子,石毛和田美夏,鈴木潤一 [他],齋藤宏,浦上達彦,高橋昌里,麦島秀雄
日大醫學雜誌 71(2), 123-128, 2012-04-01
NAID 10030565816

「メチルマロン酸」

Methylmalonic acidemia
	Classification and external resources
	; Methylmalonic acid
ICD-10	E71.1
ICD-9	270.3
OMIM	251000 251100 251110 277380 277400 277410 606169
DiseasesDB	29509 29510
MedlinePlus	001162
eMedicine	neuro/576

　　[★]

英: methylmalonic acid MMA
関: メチルマロン酸尿症、メチルマロニルCoA

HOOC-CH(CH₃)-COOH

http://en.wikipedia.org/wiki/Methylmalonic_acid
Increased methylmalonic acid levels may indicate a vitamin B12 deficiency. However, it is sensitive without being specific. *MMA is elevated in 90-98% of patients with B12 deficiency. This test may be overly sensitive, as 25-20% of patients over the age of 70 have elevated levels of MMA, but 25-33% of them do not have B12 deficiency. For this reason, MMA is not routinely recommended in the elderly.

An excess is associated with methylmalonic acidemia.

臨床関連

メチルマロン酸尿症

「メチルマロン酸血症」

　　[★]

英: methylmalonic acidemia
関: メチルマロン酸

「vitamin B12-dependent methylmalonic acidemia」

　　[★] ビタミンB12依存性メチルマロン酸血症

「methylmalonic」

　　[★]

adj.

メチルマロン酸の

関: methylmalonic acid

[1] Radmanesh, A; Zaman, T; Ghanaati, H; Molaei, S; Robertson, Rl; Zamani, Aa (July 2008). "Methylmalonic acidemia: brain imaging findings in 52 children and a review of the literature". Pediatric radiology 38 (10): 1054–61. doi:10.1007/s00247-008-0940-8. PMID 18636250.

[2] ttp://www.genome.gov/19016901

[3] Dionisi-Vici C, Deodato F, Raschinger W, Rhead W, Wilcken B (2006). "Classical organic acidurias, propionic aciduria, methylmalonic aciduria, and isovaleric aciduria: long-term outcome and effects of expanded newborn screening using tandem mass spectrometry". J Inherit Metab Dis. 29 (2-3): 383–389. doi:10.1007/s10545-006-0278-z. PMID 16763906.

[geno-4] Matsui, Sm; Mahoney, Mj; Rosenberg, Le (April 1983). "The natural history of the inherited methylmalonic acidemias" (Free full text). The New England Journal of Medicine 308 (15): 857–61. doi:10.1056/NEJM198304143081501. ISSN 0028-4793. PMID 6132336. http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+68-19-9.

[5] Sakomoto O, Ohura T, Matsubara Y, Takayanagi M, Tsuchiya S (2007). "Mutation and haplotype analyses of the MUT gene in Japanese patients with methylmalonic acidemia". J Hum Genet. 52 (1): 48–55. doi:10.1007/s10038-006-0077-2. PMID 17075691.

[6] Higginbottom MC, Sweetman L, Nyhan WL (1978). "A syndrome of methylmalonic aciduria, homocystinuria, megaloblastic anemia and neurological abnormalities in a vitamin B₁₂-deficient breast-fed infant of a strict vegetarian". N Engl J Med. 299 (7): 317–323. doi:10.1056/NEJM197808172990701. PMID 683264.

[7] ttp://www.biology.arizona.edu/biochemistry/problem_sets/b12/04t.html
Vitamin B₁₂ deficiency - The methylmalonic aciduria connection

[8] Gene identification for the cblD defect of vitamin B₁₂ metabolism. Coelho D, Suormala T, Stucki M, Lerner-Ellis JP, Rosenblatt DS, Newbold RF, Baumgartner MR, Fowler B. N Engl J Med. 2008 Apr 3;358(14):1454-64. PMID 18385497

[9] Identification of a putative lysosomal cobalamin exporter altered in the cblF defect of vitamin B₁₂ metabolism. Rutsch F, Gailus S, Miousse IR, Suormala T, Sagné C, Toliat MR, Nürnberg G, Wittkampf T, Buers I, Sharifi A, Stucki M, Becker C, Baumgartner M, Robenek H, Marquardt T, Höhne W, Gasnier B, Rosenblatt DS, Fowler B, Nürnberg P. Nat Genet. 2009 Feb;41(2):234-9. Epub 2009 Jan 11. PMID 19136951

リンク元	「メチルマロン酸」「メチルマロン酸血症」
拡張検索	「vitamin B12-dependent methylmalonic acidemia」
関連記事	「methylmalonic」

匿名

検索

案内

案内

methylmalonic acidemia