Organic acidemiais a term used to classify a group ofmetabolic disorderswhich disrupt normalamino acid metabolism,particularlybranched-chain amino acids,causing a buildup of acids which are usually not present.[1]
| Organic acidemia | |
|---|---|
| Other names | Organic aciduria, Organic acid disorder |
The branched-chain amino acids includeisoleucine,leucineandvaline.[1]Organic acidsrefer to theamino acidsand certain odd-chainedfatty acidswhich are affected by these disorders.
The four main types of organic acidemia are:methylmalonic acidemia,propionic acidemia,isovaleric acidemia,andmaple syrup urine disease.[1]
Signs and symptoms
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Cause
editMost of the organic acidemias result from defectiveautosomalgenesfor variousenzymesimportant to amino acidmetabolism.Neurological and physiological harm is caused by this impaired ability to synthesize a key enzyme required to break down a specific amino acid, or group of amino acids, resulting in acidemia and toxicity to specific organs systems. Most are inherited asautosomal recessivediseases.[2][3]
Diagnosis
editOrganic acidemias are usually diagnosed in infancy, characterized by urinary excretion of abnormal amounts or types oforganic acids.The diagnosis is usually made by detecting an abnormal pattern oforganic acidsin a urine sample bygas chromatography-mass spectrometry.In some conditions, the urine is always abnormal, in others the characteristic substances are only present intermittently. Many of the organic acidemias are detectable bynewborn screeningwith tandem mass spectrometry.[4]
These disorders vary in theirprognosis,from manageable to fatal, and usually affect more than oneorgansystem, especially thecentral nervous system.[citation needed]
Neurological damage anddevelopmental delayare common factors in diagnosis, with associated symptoms ranging frompoor feedingto slowgrowth,lethargy,vomiting, dehydration,malnutrition,hypoglycemia,hypotonia,metabolic acidosis,ketoacidosis,hyperammonemia,and if left untreated,death.[5]
Treatment
editTreatment or management of organic acidemias vary; e.g. seemethylmalonic acidemia,propionic acidemia,isovaleric acidemia,andmaple syrup urine disease.[citation needed]
As of 1984 there were no effective treatments for all of the conditions, though treatment for some included a limitedprotein/highcarbohydratediet,intravenous fluids,amino acid substitution, vitamin supplementation, carnitine, inducedanabolism,[6]and in some cases, tube-feeding.
As of 1993beta-ketothiolase deficiencyand other OAs were managed by trying to restore biochemical and physiologic homeostasis; common therapies included restricting diet to avoid the precursor amino acids and use of compounds to either dispose of toxic metabolites or increase enzyme activity.[7]
See also
edit- ACAT1 § Ketothiolase deficiency,another type of OA
References
edit- ^abcOgier de Baulny H, Saudubray JM (2002). "Branched-chain organic acidurias".Semin Neonatol.7(1):65–74.doi:10.1053/siny.2001.0087.PMID12069539.
- ^Häberle, Johannes; Boddaert, Nathalie; Burlina, Alberto; Chakrapani, Anupam; Dixon, Marjorie; Huemer, Martina; Karall, Daniela; Martinelli, Diego; Crespo, Pablo S. (2012-05-29)."Suggested guidelines for the diagnosis and management of urea cycle disorders".Orphanet Journal of Rare Diseases.7(1): 32.doi:10.1186/1750-1172-7-32.ISSN1750-1172.PMC3488504.PMID22642880.
- ^Kölker, Stefan; Christensen, Ernst; Leonard, James V.; Greenberg, Cheryl R.; Boneh, Avihu; Burlina, Alberto B.; Burlina, Alessandro P.; Dixon, Marjorie; Duran, Marinus (2011)."Diagnosis and management of glutaric aciduria type I – revised recommendations".Journal of Inherited Metabolic Disease.34(3):677–694.doi:10.1007/s10545-011-9289-5.ISSN0141-8955.PMC3109243.PMID21431622.
- ^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.PMID16763906.S2CID19710669.
- ^Pellock, John M.; Myer, Edwin C. (2013-10-22).Neurologic Emergencies in Infancy and Childhood.Butterworth-Heinemann.ISBN9781483193922.Retrieved2015-04-17.
- ^Saudubray JM, Ogier H, Charpentier C, Depondt E, Couda FX, Munnich A, Mitchell G, Rey F, Rey J, Frazal J (1984). "Hudson Memorial Lecture Neonatal Management of Organic Acidurias. Clinical Update".Organic Acidurias.Vol. 7. pp.2–9.doi:10.1007/978-94-009-5612-4_2.ISBN978-94-010-8975-3.PMID6434839.
{{cite book}}:|journal=ignored (help) - ^Seashore, MR; Pagon, RA; Adam, MP; Ardinger, HH; Bird, TD; Dolan, CR; Fong, CT; Smith, RJH; Stephens, K (1993). "The Organic Acidemias: An Overview". Gene Reviews (R) Seattle (WA): University of Washington, Seattle; 1993-2015.
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