Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162275 (ketonuria)
 553 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By means of gas chromatographic methods substantial amounts of the C6-C10-dicarboxylic acids, i.e. adipic, suberic and sebacic acids, have been found in the urine from children with unexplained attacks of lethargy and hypotonia, presumably related to episodes of fever and/or insufficient food intake. The course have once been fatal and is often characterized by severe hypoglycemia without ketonuria. Systematic gas chromatographic/mass spectrometric determinations of selected organic acid metabolites in the urine, together with enzymatic measurements in fibroblasts and clinical data from 4 patients of this category, have shown that the biochemical basis of this syndrome can be inborn errors of the beta-oxidation of fatty acids, localized to the medium-chain acyl-CoA dehydrogenation system. The biosynthesis of adipic, suberic and sebacic acids was studied using ketotic rats as the model, since ketosis in rats and humans is accompanied by excessive urinary excretion of adipic and suberic acids. A probable pathway for the production of the three dicarboxylic acids was found to be an initial omega-oxidation of the medium-chain C10-C14-monocarboxylic acids followed by beta-oxidation of the resulting medium-chain dicarboxylic acids. It is argued that the source of the omega-oxidizable monocarboxylic acids in ketosis most probably is the fat deposites, and it is speculated that the patients with beta-oxidation defects supplement this source with beta-oxidation intermediate medium-chain monocarboxylic acids, accumulated as a result of the defect. The ratio between the excreted amounts of adipic acid and sebacic acid in the urine from the patients with beta-oxidation defects is less than 50. This is in contrast to the ratio in urine from ketotic patients, where it is greater than 100. Adipic acid/sebacic acid ratio-measured by means of a gas chromatographic analysis-is therefore suggested as a tool in the diagnosis of dicarboxylic acidurias. Based on the clinical picture and the pattern of a series of organic acids in the urinary metabolic profile our four patients can be divided in two types of dicarboxylic aciduria. The two types have different therapeutic implications.
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PMID:C6-C10-dicarboxylic aciduria: biochemical considerations in relation to diagnosis of beta-oxidation defects. 695 31

Encephalopathy and Myopathy in children of varying ages can be due to variety of causes including Mitochondrial diseases, metabolic diseases like renal tubular acidosis, storage diseases as well as fatty acid oxidation (FAO) disorders. FAO related disorders have variable clinical presentation and manifest in different ages. They may present with hypoglycemia, effort intolerance, multi organ involvement with or without ketonuria. High degree of suspicion and appropriate investigations are mandatory for diagnosis. Here we describe an 11 Year old boy, born to non - consanguineous parents. Presented with exertion induced muscle pain and fatigue of 1year duration, which slowly progressed to severe weakness and vomiting. His reflexes were retained. Therefore metabolic vs inflammatory muscle diseases were considered. Patient had ketonuria with elevated blood levels of medium chain acyl carnitine and long chain acyl carnitine suggestive of MADD. Urine organic acid assessment showed elevated excretion of 2-hydroxyglutarate (2HG), adipate and arabitol. Muscle biopsy showed multiple fine vacuoles on Eosin- hematoxylin stained preparation. Modified Gomori - trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stains showed vacuolated fibers with 'oil red O' positive material suggesting lipid storage. Above combination of features is consistent of MADD. Genetic evaluation is not done due to financial constraint. Patient was started on high dose riboflavin and carnitine, with which the child became near normal. Our patient is a case of MADD presenting as Reye's syndrome like features and showed excellent response to riboflavin, carnitine, dietary and life style changes. High degree of suspicion is lifesaving.
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PMID:Lipid Storage Myopathy with Ketonuria: A Case of Fatty Acid Oxidation-Related Myopathy and Encephalopathy due to Multiple Acyl-CoA Dehydrogenase Deficiency. 3027 77