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)

A new case of propionic acidemia is presented, paying special attention to the early symptoms of this disease, such as increased drowsiness, muscular hypotonia, poor feeding, hypothermia, metabolic acidosis, ketonuria and vomiting. Investigation by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) revealed the excretion of fairly high amounts of 2-methyl-3-oxovaleric acid, a condensation product of two molecules of propionyl-CoA, as well as the known pathological metabolites such as propionic, 3-hydroxypropionic and methylcitric acids. Among the post mortem findings the histological studies of the liver were the most remarkable.
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PMID:Excretion of 2-methyl-3-oxovaleric acid in propionic acidemia. 66 27

Propionyl CoA carboxylase deficiency was found in a 7-month-old boy who presented with attacks of vomiting, anorexia, weight loss, weakness, and hypotonia. He failed to thrive and had generalized seizures. He had propionic acidemia and hyperglycinemia; these are the manifestations of the ketotic hyperglycinemia syndrome. However, ketonuria was not a consistent part of his clinical picture, and he had at least two episodes of acute overwhelming illness, the latter one fatal, in which ketones were never found in the urine. Large amounts of pyrrolidone carboxylic acid were found in body fluids.
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PMID:Hyperglycinemia and propionyl coA carboxylase deficiency and episodic severe illness without consistent ketosis. 113 51

Calcium hopantenate (HOPA) has been widely used as an activator of cerebral metabolism in Japan. However, several cases of acute encephalopathy during HOPA administration were recently reported, which were characterized by marked metabolic acidosis and hypoglycemia. The encephalopathy in these patients was named Reye-like syndrome because of the similarity to Reye's syndrome in children. The purposes of this presentation are to report on 5 patients with acute encephalopathy developing during HOPA administration, to summarize their symptoms and clinical courses, and to discuss the pathogenesis of metabolic acidosis and hypoglycemia. Initial characteristics of the clinical course in all patients were loss of appetite, nausea and vomiting, followed by unconsciousness. Laboratory examinations revealed marked metabolic acidosis, severe hypoglycemia, hyperlactacidemia, leukocytosis, ketonuria, and increased Ht and BUN. A few days after development of the initial symptoms, mild renal and liver dysfunction, and elevation of serum amylase were observed in all patients. Hyperlactacidemia was present in 4 in the initial period. Blood concentration of HOPA was 2.131 micrograms/ml in patient 1 (8-10 hours after final administration), and 10.7 micrograms/ml in patient 5 (24 hours after final administration). These values are extremely high, because usually HOPA concentration is almost negligible 7 hours after the drug is taken. As the pathogenesis of acute encephalopathy due to HOPA administration, the failure of fatty acid beta-oxidation has been proposed by some investigators. However, the serum concentrations of CoA, pantothenic acid and carnitine during the initial stage were not reduced in our patients. Furthermore, it is very difficult to explain the severe hypoglycemia in terms of the beta-oxidation theory.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Metabolic acidosis and hypoglycemia during calcium hopantenate administration--report on 5 patients]. 258 87

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

A 21-month-old infant developed coma with hypotonia during a viral infection. Acyl CoA dehydrogenase deficiency was diagnosed on the basis of results of the chromatographic study of organic acids performed on a urine specimen collected during the acute episode. However, other disorders of mitochondrial and fatty acid oxygenation can generate similar symptoms. Emphasis is put on the need for collecting urine specimens in patients who develop alterations in consciousness and hypoglycemia without ketonuria during prolonged fasting or repeated vomiting due to a viral infection. Urine chromatography can suggest which enzyme is defective, although the diagnosis should always be confirmed by a study of fatty acid oxygenation in lymphocytes or fibroblasts.
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PMID:[Deficiency in medium chain acyl coA dehydrogenase manifested as febrile coma]. 834 83

In the last decades the survival of patients with methylmalonic aciduria has been improved. However, the overall outcome of affected patients remains disappointing. The disease course is often complicated by acute life-threatening metabolic crises, which can result in multiple organ failure or even death, resembling primary defects of mitochondrial energy metabolism. Biochemical abnormalities during metabolic derangement, such as metabolic acidosis, ketonaemia/ketonuria, lactic acidosis, hypoglycaemia and hyperammonaemia, suggest mitochondrial dysfunction. In addition, long-term complications such as chronic renal failure and neurological disease are frequently found. Neuropathophysiological studies have focused on various effects caused by accumulation of putatively toxic organic acids, the so-called 'toxic metabolite' hypothesis. In previous studies, methylmalonate (MMA) has been considered as the major neurotoxin in methylmalonic aciduria, whereas more recent studies have highlighted a synergistic inhibition of mitochondrial energy metabolism (pyruvate dehydrogenase complex, tricarboxylic acid cycle, respiratory chain, mitochondrial salvage pathway of deoxyribonucleoside triphosphate (dNTP)) induced by propionyl-CoA, 2-methylcitrate and MMA as the key pathomechanism of inherited disorders of propionate metabolism. Intracerebral accumulation of toxic metabolites ('trapping' hypothesis') is considered a biochemical risk factor for neurodegeneration. Secondary effects of mitochondrial dysfunction, such as oxidative stress and impaired mtDNA homeostasis, contribute to pathogenesis of these disorders. The underlying pathomechanisms of chronic renal insufficiency in methylmalonic acidurias are not yet understood. We hypothesize that renal and cerebral pathomechanisms share some similarities, such as an involvement of dicarboxylic acid transport. This review aims to give a comprehensive overview on recent pathomechanistic concepts for methylmalonic acidurias.
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PMID:Neurodegeneration and chronic renal failure in methylmalonic aciduria--a pathophysiological approach. 1819 72

Neonatal-onset propionic acidemia (PA), the most common form, is characterized by poor feeding, vomiting, and somnolence in the first days of life in a previously healthy infant, followed by lethargy, seizures, and can progress to coma if not identified and treated appropriately. It is frequently accompanied by metabolic acidosis with anion gap, ketonuria, hypoglycemia, hyperammonemia, and cytopenias. PA is caused by deficiency of propionyl-CoA carboxylase (PCC), the enzyme that catalyzes the conversion of propionyl-CoA to methylmalonyl-CoA. Herein, we report a case of 3-day-old neonate with PA presented with acute renal failure and metabolic acidosis was effectively treated by peritoneal dialysis and conventional methods.
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PMID:Severe renal failure and hyperammonemia in a newborn with propionic acidemia: effects of treatment on the clinical course. 2432 97