Organic acidemia

Organic acidemia, also called organic aciduria, is a term used to classify a group of metabolic disorders which disrupt normal amino acid metabolism, particularly branched-chain amino acids, causing a buildup of acids which are usually not present.^[1]

The branched-chain amino acids include isoleucine, leucine and valine.^[1] Organic acids refer to the amino acids and certain odd-chained fatty acids which are affected by these disorders.

The four main types of organic acidemia are: methylmalonic acidemia, propionic acidemia, isovaleric acidemia, and maple syrup urine disease.^[1]

Diagnosis and symptoms

Organic acidemias are usually diagnosed in infancy, characterized by urinary excretion of abnormal amounts or types of organic acids. The diagnosis is usually made by detecting an abnormal pattern of organic acids in a urine sample by gas 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 by newborn screening with tandem mass spectrometry.^[2]

These disorders vary in their prognosis, from manageable to fatal, and usually affect more than one organ system, especially the central nervous system.

Neurological damage and developmental delay are common factors in diagnosis, with associated symptoms ranging from poor feeding to slow growth, lethargy, vomiting, dehydration, malnutrition, hypoglycemia, hypotonia, metabolic acidosis, ketoacidosis, hyperammonemia, and if left untreated, death.^[3]

Cause

Most of the organic acidemias result from defective autosomal genes for various enzymes important to amino acid metabolism. 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 as autosomal recessive diseases.^[4][5]

Treatment

Treatment or management of organic acidemias vary; eg see methylmalonic acidemia, propionic acidemia, isovaleric acidemia, and maple syrup urine disease.

As of 1984 there are no effective treatments for all of the conditions, though treatment for some may include a limited protein/high carbohydrate diet, intravenous fluids, amino acid substitution, vitamin supplementation, carnitine, induced anabolism,^[6] and in some cases, tube-feeding.

As of 1993 ketothiolase deficiency and other OAs are managed by trying to restore biochemical and physiologic homeostasis; common therapies include 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

• ACAT1#Ketothiolase deficiency, another type of OA

External links

• GeneReviews/UW/NIH entry on Organic acidemias
• http://www.e-imd.org/en/index.phtml

References

1. 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.
2. 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.
3. Pellock, John M.; Myer, Edwin C. (2013-10-22). Neurologic Emergencies in Infancy and Childhood. Butterworth-Heinemann. ISBN 9781483193922. Retrieved 2015-04-17.
4. 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. ISSN 1750-1172. PMC 3488504. PMID 22642880. Retrieved 2015-04-17.
5. 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. ISSN 0141-8955. PMC 3109243. PMID 21431622.
6. 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". J Inherit Metab Dis. 7 (Suppl. 1): 2–9. doi:10.1007/978-94-009-5612-4_2. PMID 6434839.
7. Seashore, MR; Pagon, RA; Adam, MP; Ardinger, HH; Bird, TD; Dolan, CR; Fong, CT; Smith, RJH; Stephens, K (1993). "The Organic Acidemias: An Overview". PMID 20301313.