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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）』「2012/12/30 11:06:26」(JST)

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Propionic acidemia, also known as propionic aciduria, propionyl-CoA carboxylase deficiency and ketotic glycinemia,^[1] is an autosomal recessive^[2] metabolic disorder, classified as a branched-chain organic acidemia.^[3]

The disorder presents in the early neonatal period with progressive encephalopathy. Death can occur quickly, due to secondary hyperammonemia, infection, cardiomyopathy, or basal ganglial stroke.^[4]

Propionic Acidemia is a rare disorder that is inherited from both parents. Being autosomal recessive, neither parent shows symptoms, but both carry a defective gene responsible for this disease. It takes two faulty genes to cause PA, so there is a 1 in 4 chance for these parents to have a child with PA.

Pathophysiology

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

In healthy individuals, the enzyme propionyl CoA carboxylase converts propionyl CoA to methylmalonyl CoA. This is one step in the process of converting certain amino acids and fats into sugar for energy. Individuals with PA cannot perform this conversion because the enzyme propionyl CoA carboxylase is nonfunctional. The essential amino acids isoleucine, valine, threonine, and methionine and odd-chain fatty acids are simply converted to propionyl CoA, before the process stops, leading to a buildup of propionyl CoA. Instead of being converted to methylmalonyl CoA, propionyl CoA is then converted into propionic acid, which builds up in the bloodstream. This in turn causes a build-up of dangerous acids and toxins, which can cause damage to the organs.

In many cases, PA can damage the brain, heart, and liver, cause seizures, and delays to normal development like walking and talking. During times of illness the affected person may need to be hospitalized to prevent breakdown of proteins within the body. Each meal presents a challenge to those with PA. If not constantly monitored, the effects would be devastating. Dietary needs must be closely managed by a metabolic geneticist or metabolic dietician.

Mutations in both copies of the PCCA or PCCB genes cause propionic acidemia.^[5] These genes are responsible for the formation of the enzyme propionyl-CoA carboxylase (EC 6.4.1.3), referred to as PCC.

PCC is required for the normal breakdown of the essential amino acids valine, isoleucine, threonine, and methionine, as well as certain odd-chained fatty-acids. Mutations in the PCCA or PCCB genes disrupt the function of the enzyme, preventing these acids from being metabolized. As a result, propionyl-CoA, propionic acid, ketones and other toxic compounds accumulate in the blood, causing the signs and symptoms of propionic acidemia.

Symptoms

Propionic acidemia is characterized almost immediately in newborns. Symptoms include poor feeding, vomiting, dehydration, acidosis, low muscle tone (hypotonia), seizures, and lethargy. The effects of propionic acidemia quickly become life-threatening.

Genetic prevalence

Propionic acidemia has an autosomal recessive pattern of inheritance.

Propionic acidemia is inherited in an autosomal recessive pattern and is found in about 1 in 35,000^[5] live births in the United States. The condition appears to be more common in Saudi Arabia,^[6] with a frequency of about 1 in 3,000.^[5] The condition also appears to be common in Amish and Mennonite populations.^[7]

References

^ Online 'Mendelian Inheritance in Man' (OMIM) 606054
^ Ravn K, Chloupkova M, Christensen E, Brandt NJ, Simonsen H, Kraus JP, Nielsen IM, Skovby F, Schwartz M (July 2000). "High incidence of propionic acidemia in greenland is due to a prevalent mutation, 1540insCCC, in the gene for the beta-subunit of propionyl CoA carboxylase". American Journal of Human Genetics 67 (1): 203–206. doi:10.1086/302971. PMC 1287078. PMID 10820128. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1287078/.
^ Deodato F, Boenzi S, Santorelli FM, Dionisi-Vici C (2006). "Methylmalonic and propionic aciduria". Am J Med Genet C Semin Med Genet. 142 (2): 104–112. doi:10.1002/ajmg.c.30090. PMID 16602092.
^ Hamilton RL, Haas RH, Nyhan WC, Powell HC, Grafe MR (1995). "Neuropathology of propionic acidemia: a report of two patients with basal ganglia lesions". Journal of Child Neurology 10 (1): 25–30. doi:10.1177/088307389501000107. PMID 7769173.
^ ^a ^b ^c http://mayoresearch.mayo.edu/mayo/research/barry_lab/ropionic-Aciademia.cfm
Barry Lab - Vector and Virus Engineering. Gene therapy for Propionic Acidemia
^ Al-Odaib AN, Abu-Amaro KK, Ozand PT, Al-Hellani AM (2003). "A new era for preventive genetic programs in the Arabian Peninsula". Saudi Medical Journal 24 (11): 1168–1175. PMID 14647548.
^ Kidd JR, Wolf B, Hsia E, Kidd KK (1980). "Genetics of propionic acidemia in a Mennonite-Amish kindred". Am J Hum Genet. 32 (2): 236–245. PMC 1686010. PMID 7386459. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1686010/.

External links

Propionic Acidemia Foundation
Organic Acidemia Association
Propionic Acidemia Research Network (PARnet)
Gwen for a Cure
Propionic acidemia at NLM Genetics Home Reference
Propionic acidemia at NIH's Office of Rare Diseases
"Propionic acidemia". Orphanet. http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=35.

UpToDate Contents

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1. 有機酸血症 organic acidemias
2. 先天性代謝異常：代謝性救急疾患 inborn errors of metabolism metabolic emergencies
3. Pathogenesis, screening, and diagnosis of neonatal hypoglycemia
4. 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
5. 先天性代謝異常：分類 inborn errors of metabolism classification

English Journal

The effect of WIN 55,212-2 suggests a cannabinoid-sensitive component in the early toxicity induced by organic acids accumulating in glutaric acidemia type I and in related disorders of propionate metabolism in rat brain synaptosomes.

Colín-González AL1, Paz-Loyola AL1, Serratos IN2, Seminotti B3, Ribeiro CA3, Leipnitz G3, Souza DO3, Wajner M4, Santamaría A5.
Neuroscience.Neuroscience.2015 Dec 3;310:578-88. doi: 10.1016/j.neuroscience.2015.09.043. Epub 2015 Sep 30.
Several physiological processes in the CNS are regulated by the endocannabinoid system (ECS). Cannabinoid receptors (CBr) and CBr agonists have been involved in the modulation of the N-methyl-d-aspartate receptor (NMDAr) activation. Glutaric (GA), 3-hydroxyglutaric (3-OHGA), methylmalonic (MMA) and
PMID 26431622

Toxic synergism between quinolinic acid and organic acids accumulating in glutaric acidemia type I and in disorders of propionate metabolism in rat brain synaptosomes: Relevance for metabolic acidemias.

Colín-González AL1, Paz-Loyola AL1, Serratos I2, Seminotti B3, Ribeiro CA3, Leipnitz G3, Souza DO3, Wajner M4, Santamaría A5.
Neuroscience.Neuroscience.2015 Nov 12;308:64-74. doi: 10.1016/j.neuroscience.2015.09.002. Epub 2015 Sep 4.
The brain of children affected by organic acidemias develop acute neurodegeneration linked to accumulation of endogenous toxic metabolites like glutaric (GA), 3-hydroxyglutaric (3-OHGA), methylmalonic (MMA) and propionic (PA) acids. Excitotoxic and oxidative events are involved in the toxic patterns
PMID 26343296

Heptadecanoylcarnitine (C17) a novel candidate biomarker for newborn screening of propionic and methylmalonic acidemias.

Malvagia S1, Haynes CA2, Grisotto L3, Ombrone D1, Funghini S1, Moretti E4, McGreevy KS5, Biggeri A3, Guerrini R6, Yahyaoui R7, Garg U8, Seeterlin M9, Chace D10, De Jesus VR2, la Marca G11.
Clinica chimica acta; international journal of clinical chemistry.Clin Chim Acta.2015 Oct 23;450:342-8. doi: 10.1016/j.cca.2015.09.012. Epub 2015 Sep 11.
BACKGROUND: 3-Hydroxypalmitoleoyl-carnitine (C16:1-OH) has recently been reported to be elevated in acylcarnitine profiles of patients with propionic acidemia (PA) or methylmalonic acidemia (MMA) during expanded newborn screening (NBS). High levels of C16:1-OH, combined with other hydroxylated long
PMID 26368264

Japanese Journal

臨床研究・症例報告著明な高アンモニア血症で発症し,代謝性アシドーシスは呈さなかったプロピオン酸血症の1例

菅野潤子,坂本修,鎌田文顕 [他]
小児科臨床 64(8), 1857-1863, 2011-08
NAID 40018896101

Propionic acidemia mimicking diabetic ketoacidosis

DWEIKAT Imad M.,NASER Enas N.,ABU LIBDEH Abdulsalam I.,NASER Osama J.,ABU GHARBIEH Najwan N.,MARAQA Nizar F.,ABU LIBDEH Bassam Y.
Brain & development 33(5), 428-431, 2011-05-01
NAID 10029561795

Related Pictures

★リンクテーブル★

リンク元	「プロピオン酸」「アミノ酸代謝異常症」「プロピオン酸血症」

「プロピオン酸」

Propionic acidemia
	Classification and external resources
	; Propionic acid
ICD-10	E71.1
ICD-9	270.3
OMIM	606054
DiseasesDB	29673 29904
eMedicine	ped/1906

　　[★]

英: propionic acid
同: プロパン酸、プロパン
関: カルボン酸

http://ja.wikipedia.org/wiki/%E3%83%97%E3%83%AD%E3%83%94%E3%82%AA%E3%83%B3%E9%85%B8
C3H6O2
CH3-CH2-COOH

プロピオン酸（プロピオンさん、propionic acid）は示性式CH₃CH₂COOH、分子量74.08のカルボン酸。IUPAC命名法ではプロパン酸 (propanoic acid) となる。CAS登録番号は79-09-4。

物性

単体は融点−21℃、沸点141℃の無色の液体で、不快な臭気を有する。水、エタノール、クロロホルム、エーテルなどに溶けやすい。1-プロパノール、プロピオンアルデヒドの酸化によって得られる。

反芻動物におけるプロピオン酸

反芻胃で食物の中のセルロースやヘミセルロースを嫌気発酵して、プロピオン酸などの短鎖脂肪酸を生成している。

ヒト(非反芻動物を含む)におけるプロピオン酸

奇数脂肪酸のβ酸化、イソロイシンとコレステロール側鎖の酸化によって得られる。(HBC.169)

代謝

HBC. 169

プロピオン酸　＋　CoA-SH　＋　ATP　－－(acyl-CoA synthetase + Mg2+)－→　AMP　＋　PPi　＋　プロピオニルCoA
プロピオニルCoA　＋　CO2　＋　H2O　＋　ATP　－－(propionyl-CoA carboxylase+ビオチン)－→　D-メチルマロニルCoA　＋　ADP　＋　Pi

→プロピオン酸血症

D-メチルマロニルCoA　－－(methylmalonyl-CoA racemase)－→　L-メチルマロニルCoA
L-メチルマロニルCoA　－－(methylmalonyl-CoA isomerase/methylmalonyl-CoA mutase+ビタミンB12)－→　サクシニルCoA

→メチルマロン酸尿症

誘導体

イブプロフェン、ナプロキセン、ロキソプロフェンナトリウムなど、Α炭素に芳香族部位が置換した非ステロイド性抗炎症薬 (NSAIDs) が知られ、「プロピオン酸系」と称される。

臨床関連

「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

「プロピオン酸血症」

　　[★]

英: propionic acidemia
同: プロピオニルCoAカルボキシラーゼ欠損症 propionyl-CoA carboxylase deficiency
関: プロピオニルCoAカルボキシラーゼ、プロピオン酸、プロピオン酸尿症

[1] Online 'Mendelian Inheritance in Man' (OMIM) 606054

[2] Ravn K, Chloupkova M, Christensen E, Brandt NJ, Simonsen H, Kraus JP, Nielsen IM, Skovby F, Schwartz M (July 2000). "High incidence of propionic acidemia in greenland is due to a prevalent mutation, 1540insCCC, in the gene for the beta-subunit of propionyl CoA carboxylase". American Journal of Human Genetics 67 (1): 203–206. doi:10.1086/302971. PMC 1287078. PMID 10820128. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1287078/.

[oad-3] Deodato F, Boenzi S, Santorelli FM, Dionisi-Vici C (2006). "Methylmalonic and propionic aciduria". Am J Med Genet C Semin Med Genet. 142 (2): 104–112. doi:10.1002/ajmg.c.30090. PMID 16602092.

[pbg-4] Hamilton RL, Haas RH, Nyhan WC, Powell HC, Grafe MR (1995). "Neuropathology of propionic acidemia: a report of two patients with basal ganglia lesions". Journal of Child Neurology 10 (1): 25–30. doi:10.1177/088307389501000107. PMID 7769173.

[pamr-5] ttp://mayoresearch.mayo.edu/mayo/research/barry_lab/ropionic-Aciademia.cfm
Barry Lab - Vector and Virus Engineering. Gene therapy for Propionic Acidemia

[pasa-6] Al-Odaib AN, Abu-Amaro KK, Ozand PT, Al-Hellani AM (2003). "A new era for preventive genetic programs in the Arabian Peninsula". Saudi Medical Journal 24 (11): 1168–1175. PMID 14647548.

[paam-7] Kidd JR, Wolf B, Hsia E, Kidd KK (1980). "Genetics of propionic acidemia in a Mennonite-Amish kindred". Am J Hum Genet. 32 (2): 236–245. PMC 1686010. PMID 7386459. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1686010/.

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案内

propionic acidemia