Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congenital methylmalonic aciduria (MMA) is a metabolic disorder inherited by an autosomal recessive trait. The metabolic block is located in the catabolic pathway of propionyl-CoA to succinyl-CoA. Biochemically, four enzymatic defects have been recognized, i.e.: 1. Methylmalonyl-CoA racemase. 2. Methylmalonyl-CoA mutase apoenzyme. 3. Synthesis of desoxyadenosyl-cobalamine. 4. Disturbance at an earlier level of cobalamine metabolism which causes defective synthesis of both vitamin B12-coenzymes. These four enzymatic defects express themselves in three ways: non-vitamin B12-dependent MMA (defects 1 and 2); vitamin B12-dependent MMA (defect 3); MMA associated with homocystinuria (defect 4). The various forms of MMA cannot be distinguished clinically from one another. The disorder manifests itself during the first few days to weeks of life. Principal symptoms and signs are: anorexia, vomiting, muscular hypotonia and metabolic acidosis. The diagnosis is established by determination of methylmalonic acid in plasma, cerebrospinal fluid and urine, as well as by assay of enzyme activities in leukocytes, liver tissue or cultured fibroblasts (from biopsied skin). A prenatal diagnosis is feasible by the examination of cultured amnion cells, amniotic fluid and maternal urine. Therapy of non vitamin B12-dependent MMA calls for reduction of protein intake, particularly that of precursors of methylmalonic acid, such as methionine, threonine, isoleucine and valine. The treatment of vitamin B12-dependent forms is accomplished by i.m. injection of high doses of vitamin B12. No definite statement can be made as yet with regard to long-term prognosis and normalcy of mental development in treated children.
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PMID:[Methylmalonic aciduria. Classification, diagnosis and therapy (author's transl)]. 31 93

The mechanisms underlying ethylmalonic-adipic aciduria were studied in a 5-yr-old girl. Oxidation of radioactive substrates by cultured skin fibroblasts from the proband and asymptomatic family members was also determined and compared to that by normal fibroblasts and that by cells from a patient with glutaric aciduria type II. Feeding medium-chain triglycerides promptly induced vomiting and lethargy accompanied by a pronounced increase of urinary ethylmalonate. Significant increases of serum isovalerate and urinary isovalerylglycine were observed after leucine feeding, but urinary glutarate increased only slightly after lysine feeding. Thus, the results from clinical investigation remained equivocal as to whether pathways other than fatty acid oxidation were blocked in our patient. Oxidation of [1-(14)C]butyrate by cultured skin fibroblasts from the proband was reduced to 14% of control. In vitro oxidation of [2-(14)C]lysine and [2-(14)C]leucine was also reduced to 28 and 23% of control, respectively. Much more severe reduction in oxidation of these three substrates (3, 9, and 9%, respectively) was observed in glutaric aciduria type II cells. These results indicated that in the proband, degradative pathways of fatty acids, lysine, and leucine are blocked at the steps of butyryl-CoA, glutaryl-CoA, and isovaleryl-CoA dehydrogenases, respectively, as in the case of glutaric aciduria type II. Because activities of multiple acyl-CoA dehydrogenases are reduced, a deficiency of electron-transferring flavoprotein, which serves as a hydrogen-acceptor for these dehydrogenases, is postulated as the underlying mechanisms of these two diseases, but a genetic heterogeneity was indicated by significant differences in the residual activities in these two types of cells. The hypothesis of more than one mutant allele of an autosomal recessive gene was also suggested by the study on cells from asymptomatic members of the family.
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PMID:Ethylmalonic-adipic aciduria. In vivo and in vitro studies indicating deficiency of activities of multiple acyl-CoA dehydrogenases. 50 Aug 26

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

Hypoglycin A is a toxin which causes Jamaican vomiting sickness. In rats treated with this compound, we observed significant increases in a number of amino acids in the plasma and the urine, and detected several unidentified amino compounds in the urine. These changes suggest that hypoglycin, in addition to its known inhibitory effect on acyl-CoA dehydrogenases interferes with some steps in nitrogen metabolism as well. The amino acid abnormalities seen in hypoglycin-treated rats are compared with those seen in Reye's syndrome.
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PMID:Plasma and urine amino acid changes in rats treated with hypoglycin. 69 43

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

Propionic acidemia is a rare hereditary disease which is an autosomal recessive disorder. Defect of propionyl CoA carboxylase results in abnormal accumulation of propionate and its metabolites which interfere the pathway of glycine cleavage and the urea cycle. This organic acidemia is characterized by a wide spectrum of clinical and biochemical findings, including recurrent vomiting, difficult feeding, lethargy, hypotonia, metabolic ketoacidosis, hyperglycinemia and hyperammonemia during the acute episodes. We present a male newborn infant who sustained this disorder and was managed successfully with blood exchange transfusion, peritoneal dialysis, supplemented with sodium benzoate and sodium bicarbonate therapy. Urine gas chromatography disclosed significant elevation of propionate and its metabolites which subsided 2 days after peritoneal dialysis. Special designed formula was then given with restriction of protein intake and supplement with sodium benzoate and sodium carbonate. Prenatal genetic counseling is necessary in further pregnancy. Diagnosis can be obtained when propionyl CoA carboxylase activity is low in cultured amniotic fluid cells or chorion villi sample or when there is abnormally high methylcitrate level in amniotic fluid.
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PMID:[Propionic acidemia: report of a case that is successfully managed by peritoneal dialysis and sodium benzoate therapy]. 217 70

To date, seven inborn errors of mitochondrial fatty acid oxidation have been identified. A total of about 100 patients in the world have been reported. Clinically the beta-oxidation defects are more often characterized by episodic hypoglycaemia leading to a coma mimicking Reye's syndrome. The hypoglycaemia is non-ketotic since the synthesis of ketone bodies is deficient. Periods of decompensation occur when carbohydrate supply is poor, e.g. prolonged fasting, vomiting, or increased caloric requirements, as and when lipid stores are used. Defects in beta-oxidation have also been reported to be one cause of sudden infant death syndrome. The diagnosis of these inborn errors is by biochemical investigation since where symptoms suggest such a defect, the precise aetiology cannot be assessed. The biochemical diagnosis is based firstly on identification of abnormal plasma and of urinary metabolites during acute attacks. Derivatives of the omega-oxidation and omega-1-oxidation of medium chain fatty acids have been identified, as well as acylglycine and acylcarnitine conjugates. These metabolites are nearly always absent when patients are in good clinical condition. Secondly, the diagnosis must be based on the identification of the enzymatic defects: this involves global assays which allow a localization of the 'level' of the defect (i.e. the oxidation of long, medium or short chain fatty acids) and specific measurement of enzyme activities (acyl-CoA dehydrogenases and electron carriers: ETF and ETF-DH). The diagnosis of these disorders is of prime importance because of the severity of the clinical symptoms. These can be prevented, in some cases, by an appropriate diet (a high carbohydrate, low fat diet, sometimes supplemented with L-carnitine). In other cases, genetic counselling can be offered.
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PMID:The inborn errors of mitochondrial fatty acid oxidation. 311 38

A second child with a more severe deficiency of malonyl CoA decarboxylase is described. He is mildly mentally retarded and presented with vomiting, a seizure, hypoglycaemia and mild metabolic acidosis during a urinary tract infection. The urine contained increased amounts of malonic, methylmalonic, succinic, adipic, glutaric and suberic acids. Mitochondrial malonyl CoA decarboxylase activity in cultured fibroblast extracts was 4% of the mean control value. A high fat, low carbohydrate diet led to symptomatic hypoglycaemia, a moderate metabolic acidosis and excretion in the urine of large amounts of the same organic acids and 3-hydroxybutyrate. Only relatively small quantities of malonic, methylmalonic and succinic acid were excreted in the urine when the boy was fed an isocaloric low fat, high carbohydrate diet. Acute fat and lysine loads led to increased excretion of malonic acid in the urine without affecting the excretion of the other organic acids. Experience with this patient suggests that malonyl CoA decarboxylase serves an important function in the mitochondrion by preventing accumulation of malonyl CoA. The importance of the enzyme is best seen when fat is the main metabolic fuel. The mechanisms by which malonyl CoA produces its complex metabolic effects remain to be elucidated.
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PMID:Malonyl coenzyme A decarboxylase deficiency. Clinical and biochemical findings in a second child with a more severe enzyme defect. 370 68

Evidence is presented for the specific in vivo and in vitro inhibition of isovaleryl CoA dehydrogenation by hypoglycin A and its derivative, alpha-ketomethylenecyclopropylpropionic acid. alpha-Methylbutyryl CoA dehydrogenation was also impaired, but the degree of inhibition was much lower. Isobutyryl CoA dehydrogenation was not inhibited. 4-Pentenoic acid inhibited none of these reactions. It is concluded that isovaleryl CoA is dehydrogenated by a specific enzyme, isovaleryl CoA dehydrogenase, contrary to previous assumptions that it is dehydrogenated by green acyl CoA dehydrogenase. The present concept agrees with our previous findings in isovaleric acidemia, a genetic disorder in which a specific defect of isovaleryl CoA dehydrogenase was observed. It was also demonstrated that isovaleric acidemia can be induced in experimental animals by the administration of hypoglycin A. Furthermore, some symptoms of "the vomiting sickness of Jamaica" appear to be due to isovaleric acid accumulation secondary to the ingestion of hypoglycin A.
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PMID:Hypoglycin A: a specific inhibitor of isovaleryl CoA dehydrogenase. 527 92

Congenital methylmalonic acidaemia (MMA-aemia) was diagnosed in an 8-month-old girl who presented with severe metabolic acidosis, hypoglycaemia and hyperglycinaemia. Vomiting, failure to thrive and apathy first appeared when breast feeding was replaced by a cows' milk formula at the age of 3 months. The patient, unresponsive to OH-Cbl therapy, was successfully treated with dietary protein restriction and with Shohl's solution. Aged 4 years 9 months, she is in good health. Studies in cultured fibroblasts revealed a defect of the MMA-CoA mutase apoenzyme. Mutase activity in cell extracts was barely detectable both with and without added coenzyme (Ado-Cbl). Addition of OH-Cbl to the culture medium improved overall propionate metabolism in intact fibroblasts but had no effect on mutase activity in cell extracts. These observations point to the presence of a very labile mutant enzyme, suggesting that the patient reported here may be suffering from yet another variant of MMA-aemia.
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PMID:Methylmalonic acidaemia due to mutase apoenzyme defect: responsive to vitamin B12 in intact fibroblasts but not in vivo. 613 33


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