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

A case of sudden death associated with fatty liver and encephalopathy is described in a 4-year old white boy with medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency. The death was caused by hypoglycemia triggered by fasting and vomiting associated with a minor viral infection. The differential diagnosis of the hepatoencephalopathy is discussed in relation to other conditions, especially Reye's syndrome. The forensic pathologist should be familiar with MCAD and other deficiencies of beta-oxidation of fatty acids as a cause of sudden unexpected death in children in order to advise parents in genetic counseling to prevent disability or death of other affected, but still asymptomatic siblings.
 ...
PMID:Fatty liver, encephalopathy, and sudden unexpected death in early childhood due to medium-chain acyl-coenzyme A dehydrogenase deficiency. 128 65

Treatment of 17 children aged 2-9.5 years with a combination of pivmecillinam and pivampicillin (250-500 mumol 24 h-1) for more than 1 year resulted in a reduction of the free carnitine concentration in serum and muscle to less than 10% of the mean reference value. The decline in serum was slow, with an estimated half-life of about 5 months. Spontaneous replenishment occurred at about the same slow rate. Thus, there is no increase in endogenous carnitine synthesis as a response to increased demand of carnitine for detoxification. Supplementation with carnitine during treatment required at least a four-fold molar excess over pivalic acid to achieve and sustain a normal carnitine concentration. The replenishment of carnitine occurred with a half-life of 1.1-3.0 months. From determination of muscle-carnitine concentration in patients treated with pivaloyl-containing antibiotics and in patients with organic aciduris, we conclude that serum carnitine is a good predictor of carnitine stores in the body. Six non-supplemented patients with a serum free-carnitine concentration of 0.7-2.6 mumol l-1 had an inadequate ketone-body increase during a 24-h fast. Vomiting, nausea and tiredness occurred in three cases following the fasting period. After normalization of the serum-carnitine concentration, a normal response to fasting was observed. Thus, in some organic acidurias, for example medium-chain acyl-CoA dehydrogenase deficiency, a low liver concentration of carnitine may be an important contributing factor to hypoglycaemic and Reye-like attacks. We believe that prodrugs which contain pivalic acid should be avoided if acceptable alternatives exist. If used, supplementation with at least four-fold molar excess of carnitine is advisable.
 ...
PMID:Effects of pivalic acid-containing prodrugs on carnitine homeostasis and on response to fasting in children. 151 15

From 65 reported cases of medium chain acyl-CoA dehydrogenase deficiency, we found an average presenting age of 13.5 months and a mean age at death of 18.5 months. One quarter of patients died of a Reye-like syndrome and/or sudden infant death. In half the cases there had been at least one sibling death. Asymptomatic cases were not uncommon (12% of cases). The crises were generally induced by a prolonged fast and after a viral prodromal phase in three quarters of cases. The crises consisted of somnolence progressing to lethargy which could lead to coma. Vomiting was frequent (60% of cases). Seizures, which were found in 29% of cases, represented a bad prognosis. The physical examinations revealed frequently a variable and regressive anicteric hepatomegaly. Blood and urine analysis revealed in most instances hypoglycaemia (96% of cases) with hypoketonuria and sometimes metabolic acidosis. Hepatic and muscular cytolytic enzymes were frequently raised, as were plasma ammonia, urea, and uric acid. Plasma total or free carnitine concentrations, especially non-fasting, were diminished in most cases. Plasma saturated medium chain fatty acids and particularly unsaturated cis-4-decenoate were on the other hand raised during the crises or during fasting. Urinary organic acid analysis revealed a characteristic profile of medium chain aciduria: C6-C10 dicarboxylic acids, hydroxy acids, glycine conjugates, and carnitine conjugates. Oral loading tests with carnitine or phenylpropionate allow a precise diagnosis. The diagnosis is confirmed by specific assays in various tissues. Avoidance of prolonged fasting seems to be the mainstay of treatment.
 ...
PMID:Medium chain acyl-CoA dehydrogenase deficiency. 173 32

A case of severe hypoglycaemia precipitated by fasting in a child is described. As a result of the hypoglycaemia, the patient became brain damaged. The mechanism causing the hypoglycaemia was a defect in the fatty acid beta-oxidation enzyme, the connecting link acyl-CoA dehydrogenase. During a prolonged fast, fatty acids are not converted to acetyl-CoA and ketone bodies which participate in Kreb's cycle for production of energy to a sufficient extent. This result in non-ketotic hypoglycaemia with excretion of organic acids in the urine. As a rule, the symptoms occur for the first time during the first to second years of life in connection with common infectious diseases, with vomiting followed by clouding of consciousness and possibly coma, but the condition may also present with sudden unexpected death. Treatment consists of intravenous glucose. The diagnosis is established by testing the urine for hexanoylglycin and other substances and is confirmed by culture of skin fibroblasts and measurement of beta-oxidation activity. The disease is an autosomally recessive inherited condition. In families where there have been cases of unexplained hypoglycaemia and clouding of consciousness and cases of unexplained death in infancy or "near misses", all of the family members should be offered examination for the above mentioned enzyme deficiency.
 ...
PMID:[Severe hypoglycemia and clouding of consciousness caused by deficiency of the connecting link acyl CoA dehydrogenase]. 200 Jun 54

Two siblings are reported who were symptomatic in the neonatal period. The first died suddenly at 4 days of age after regurgitating a meal. The postmortem examination showed steatosis of the liver, kidney and muscle. In the second, medium-chain acyl-CoA dehydrogenase (MCAD) deficiency was diagnosed at 3 days of age with muscular hypotonia, vomiting, hyperammonaemia and mild acidosis. Thus disorders of fatty acid oxidation should also be considered in newborns. The biochemical work up indicates that in neonates, analysis of serum medium-chain fatty acids and of acyl and free carnitine are more likely to lead to a diagnosis than determining dicarboxylic acids alone in urine. Long-term treatment was effective and monitored by the acyl/free carnitine ratio.
 ...
PMID:Early diagnosis and treatment of neonatal medium-chain acyl-CoA dehydrogenase deficiency: report of two siblings. 234 56

Medium-chain acyl-CoA dehydrogenase deficiency is a recently described inborn error of metabolism characterized by episodes of coma and hypoketotic hypoglycaemia in response to prolonged fasting. Secondary carnitine deficiency has been documented in these patients as well as the excretion in the urine of medium-chain-length acyl carnitine esters, such as octanoylcarnitine. Based on the potential toxicity of medium-chain fatty acid metabolites and the beneficial responses of patients with other inborn errors of metabolism and secondary carnitine deficiency, oral carnitine has been proposed as treatment for children with medium-chain acyl-CoA dehydrogenase deficiency. We report the results of carefully monitored fasting challenges of an infant with this deficiency both before and after 3 months of oral carnitine therapy. Carnitine supplementation failed to prevent lethargy, vomiting, hypoglycaemia and accumulation of free fatty acids in response to fasting despite normalization of plasma carnitine levels and a marked increase in urinary excretion of acyl-carnitine esters. Potentially toxic medium-chain fatty acids accumulated in the plasma in spite of therapy. Based on this study of one patient, we stress that avoidance of fasting and prompt institution of glucose supplementation in situations when oral intake is interrupted remain the mainstays of therapy for medium-chain acyl-CoA dehydrogenase deficient patients.
 ...
PMID:Medium-chain acyl-CoA dehydrogenase deficiency: metabolic effects and therapeutic efficacy of long-term L-carnitine supplementation. 250 71

Genetic deficiency of short-chain acyl-coenzyme A (CoA) dehydrogenase activity was demonstrated in cultured fibroblasts from a 2-yr-old female whose early postnatal life was complicated by poor feeding, emesis, and failure to thrive. She demonstrated progressive skeletal muscle weakness and developmental delay. Her plasma total carnitine level (35 nmol/ml) was low-normal, but was esterified to an abnormal degree (55% vs. control of less than 10%). Her skeletal muscle total carnitine level was low (7.6 nmol/mg protein vs. control of 14 +/- 2 nmol/mg protein) and was 75% esterified. Mild lipid deposition was noted in type I muscle fibers. Fibroblasts from this patient had 50% of control levels of acyl-CoA dehydrogenase activity towards butyryl-CoA as substrate at a concentration of 50 muM in a fluorometric assay based on the reduction of electron transfer flavoprotein. All of this residual activity was inhibited by an antibody against medium-chain acyl-CoA dehydrogenase. These data demonstrated that medium-chain acyl-CoA dehydrogenase accounted for 50% of the activity towards the short-chain substrate, butyryl-CoA, under these conditions, but that antibody against that enzyme could be used to unmask the specific and virtually complete deficiency of short-chain acyl-CoA dehydrogenase in this patient. Fibroblasts from her parents had intermediate levels of activity towards butyryl-CoA, consistent with the autosomal recessive inheritance of this metabolic defect.
 ...
PMID:Genetic deficiency of short-chain acyl-coenzyme A dehydrogenase in cultured fibroblasts from a patient with muscle carnitine deficiency and severe skeletal muscle weakness. 333 34

A family is described in which the father and three (and probably all four) of his children had a decreased capacity for the oxidation of medium-chain fatty acids. One of the children suddenly died at the age of 16 months following an episode of a rapidly deteriorating Reye syndrome-like illness with hypoketotic hypoglycemia and dicarboxylic aciduria, but without any previous alarming symptoms. The eldest sibling had died at the age of 19 months under similar conditions. The other family members had always been healthy. On fasting, all affected family members accumulated in their plasma the medium-chain fatty acids octanoic, decanoic, and cis-4-decenoic acids. Their urinary organic acid excretion profile could be characterized as "dicarboxylic aciduria." A deficiency of medium-chain acyl-coenzyme A dehydrogenase was demonstrated in a postmortem liver sample of the index patient. Cultured fibroblasts from the father and the two healthy children had a decreased rate of [14C]octanoate oxidation. It is suggested that a deficiency of medium-chain acyl-coenzyme A dehydrogenase may lead to a life-threatening illness when other complicating factors such as diarrhea and vomiting result in an abnormal depletion of the body's glycogen stores. Careful monitoring of at-risk patients during a minor illness is necessary.
 ...
PMID:Sudden child death and 'healthy' affected family members with medium-chain acyl-coenzyme A dehydrogenase deficiency. 378 30

Five patients aged 7 to 21 months are described who developed attacks of coma after a short prodromal illness with diarrhea or vomiting or both. Four had concomitant hypoglycemia, and all had hypoketonemia, with excessive urinary excretion of medium-chain dicarboxylic acids, medium-chain (omega-1)-hydroxyacids, suberylglycine, hexanoylglycine, and octanoylcarnitine. All patients accumulated octanoic acid, decanoic acid, and cis-4-decenoic acid in plasma. Fibroblasts from three patients showed a decreased rate of octanoate oxidation (10%, 12%, and 29% of control values, respectively). These findings suggest a deficiency of medium-chain acyl-CoA dehydrogenase, most probably an autosomal recessive inherited metabolic disorder. Two of the patients died during an acute attack, and a third had severe neurologic sequelae; the two remaining patients recovered. Plasma free carnitine levels were low, but total carnitine was normal. The three surviving patients underwent a fasting test, which did not lead to hypoglycemia, although hypoketonemia, dicarboxylic aciduria, and excessive mobilization of fatty acids did occur. The surviving patients were maintained on frequent carbohydrate-enriched meals.
 ...
PMID:Octanoic acidemia and octanoylcarnitine excretion with dicarboxylic aciduria due to defective oxidation of medium-chain fatty acids. 403 35

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.
 ...
PMID:Hypoglycin A: a specific inhibitor of isovaleryl CoA dehydrogenase. 527 92


1 2 3 Next >>