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]

Contents 1 Diagnosis and Symptoms 2 Cause 3 Treatment 4 External links 5 References

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.

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.

Treatment

Treatment or management of organic acidemias vary. 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,^[3] and in some cases, tube-feeding.

External links

• GeneReviews/UW/NIH entry on Organic acidemias

http://www.oaanews.org - Organic Acidemia Association - Parent Support Group for organic acid disorders.

References

Inborn error of amino acid metabolism (E70–E72, 270) K→acetyl-CoA Lysine/straight chain Glutaric acidemia type 1 · type 2 · Hyperlysinemia · Pipecolic acidemia · Saccharopinuria Leucine Maple syrup urine disease · Isovaleric acidemia · 3-Methylcrotonyl-CoA carboxylase deficiency · 3-hydroxy-3-methylglutaryl-CoA lyase deficiency · 3-Methylglutaconic aciduria 1 Tryptophan Hypertryptophanemia G G→pyruvate→citrate Glycine Sarcosinemia · D-Glyceric acidemia · Glutathione synthetase deficiency Glycine→Creatine: GAMT deficiency · Glycine encephalopathy G→glutamate→ α-ketoglutarate Histidine Carnosinemia · Histidinemia · Urocanic aciduria Proline Hyperprolinemia · Prolidase deficiency Glutamate/glutamine SSADHD G→propionyl-CoA→ succinyl-CoA Valine Maple syrup urine disease · Hypervalinemia · Isobutyryl-CoA dehydrogenase deficiency Isoleucine Maple syrup urine disease · Beta-ketothiolase deficiency · 2-Methylbutyryl-CoA dehydrogenase deficiency Methionine Hypermethioninemia · Homocystinuria · Cystathioninuria General BC/OA Propionic acidemia · Methylmalonic acidemia · Methylmalonyl-CoA mutase deficiency G→fumarate Phenylalanine/tyrosine Phenylketonuria Tetrahydrobiopterin deficiency · 6-Pyruvoyltetrahydropterin synthase deficiency Tyrosinemia Type II tyrosinemia · Type III tyrosinemia/Hawkinsinuria · Alkaptonuria/Ochronosis · Type I tyrosinemia Tyrosine→Melanin Albinism: Ocular albinism (1) · Oculocutaneous albinism (Hermansky–Pudlak syndrome) · Waardenburg syndrome Tyrosine→Norepinephrine Dopamine beta hydroxylase deficiency · reverse: Brunner syndrome G→oxaloacetate Urea cycle/Hyperammonemia (arginine, aspartate) N-Acetylglutamate synthase deficiency · Carbamoyl phosphate synthetase I deficiency · Ornithine transcarbamylase deficiency/translocase deficiency · Citrullinemia · Argininosuccinic aciduria · Argininemia Transport/ IE of RTT Solute carrier family: Cystinuria · Hartnup disease · Lysinuric protein intolerance · Iminoglycinuria Fanconi syndrome: Oculocerebrorenal syndrome · Cystinosis Other Trimethylaminuria · 2-Hydroxyglutaric aciduria · Fumarase deficiency M: MET mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon m(A16/C10),i(k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)