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.
The four main types of organic acidemia are: methylmalonic acidemia, propionic acidemia, isovaleric acidemia, and maple syrup urine disease.
Organic acids refer to the amino acids and certain odd-chained fatty acids which are affected by these disorders.
The branched-chain amino acids include isoleucine, leucine and valine.
Diagnosis and Symptoms
Organic acidemias are usually always 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.
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.
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 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, and in some cases, tube-feeding.
- ^ a b c Ogier de Baulny H, Saudubray JM (2002). "Branched-chain organic acidurias". Semin Neonatol. 7 (1): 65-74. PMID 12069539.
- ^ 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. PMID 16763906.
- ^ 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. PMID 6434839.
|Metabolic pathology / Inborn error of metabolism (E70-90, 270-279)|
|Amino acid||Aromatic (Phenylketonuria, Alkaptonuria, Ochronosis, Tyrosinemia, Albinism, Histidinemia) - Organic acidemias (Maple syrup urine disease, Propionic acidemia, Methylmalonic acidemia, Isovaleric acidemia, 3-Methylcrotonyl-CoA carboxylase deficiency) - Transport (Cystinuria, Cystinosis, Hartnup disease, Fanconi syndrome, Oculocerebrorenal syndrome) - Sulfur (Homocystinuria, Cystathioninuria) - Urea cycle disorder (N-Acetylglutamate synthase deficiency, Carbamoyl phosphate synthetase I deficiency, Ornithine transcarbamylase deficiency, Citrullinemia, Argininosuccinic aciduria, Hyperammonemia) - Glutaric acidemia type 1 - Hyperprolinemia - Sarcosinemia|
|Carbohydrate||Lactose intolerance - Glycogen storage disease (type I, type II, type III, type IV, type V, type VI, type VII) - fructose metabolism (Fructose intolerance, Fructose bisphosphatase deficiency, Essential fructosuria) - galactose metabolism (Galactosemia, Galactose-1-phosphate uridylyltransferase galactosemia, Galactokinase deficiency) - other intestinal carbohydrate absorption (Glucose-galactose malabsorption, Sucrose intolerance) - pyruvate metabolism and gluconeogenesis (PCD, PDHA) -
Pentosuria - Renal glycosuria|
|Lipid storage||Sphingolipidoses/Gangliosidoses: GM2 gangliosidoses (Sandhoff disease, Tay-Sachs disease) - GM1 gangliosidoses - Mucolipidosis type IV - Gaucher's disease - Niemann-Pick disease - Farber disease - Fabry's disease - Metachromatic leukodystrophy - Krabbe disease|
Neuronal ceroid lipofuscinosis (Batten disease) - Cerebrotendineous xanthomatosis - Cholesteryl ester storage disease (Wolman disease)
|Fatty acid metabolism||Lipoprotein/lipidemias: Hyperlipidemia - Hypercholesterolemia - Familial hypercholesterolemia - Xanthoma - Combined hyperlipidemia - Lecithin cholesterol acyltransferase deficiency - Tangier disease - Abetalipoproteinemia |
Fatty acid: Adrenoleukodystrophy - Acyl-coA dehydrogenase (Short-chain, Medium-chain, Long-chain 3-hydroxy, Very long-chain) - Carnitine (Primary, I, II)
|Mineral||Cu Wilson's disease/Menkes disease - Fe Haemochromatosis - Zn Acrodermatitis enteropathica - PO43�' Hypophosphatemia/Hypophosphatasia - Mg2+ Hypermagnesemia/Hypomagnesemia - Ca2+ Hypercalcaemia/Hypocalcaemia/Disorders of calcium metabolism|
and acid-base balance
|Electrolyte disturbance - Na+ Hypernatremia/Hyponatremia - Acidosis (Metabolic, Respiratory, Lactic) - Alkalosis (Metabolic, Respiratory) - Mixed disorder of acid-base balance - H2O Dehydration/Hypervolemia - K+ Hypokalemia/Hyperkalemia - Cl�' Hyperchloremia/Hypochloremia|
|Purine and pyrimidine||Hyperuricemia - Lesch-Nyhan syndrome - Xanthinuria|
|Porphyrin||Acute intermittent, Gunther's, Cutanea tarda, Erythropoietic, Hepatoerythropoietic, Hereditary copro-, Variegate|
|Bilirubin||Unconjugated (Lucey-Driscoll syndrome, Gilbert's syndrome, Crigler-Najjar syndrome) - Conjugated (Dubin-Johnson syndrome, Rotor syndrome)|
|Glycosaminoglycan||Mucopolysaccharidosis - 1:Hurler/Hunter - 3:Sanfilippo - 4:Morquio - 6:Maroteaux-Lamy - 7:Sly|
|Glycoprotein||Mucolipidosis - I-cell disease - Pseudo-Hurler polydystrophy - Aspartylglucosaminuria - Fucosidosis - Alpha-mannosidosis - Sialidosis|
|Other||Alpha 1-antitrypsin deficiency - Cystic fibrosis - Amyloidosis (Familial Mediterranean fever) - Acatalasia|