Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.99.3 (acyl-CoA dehydrogenase)
 1,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prevalence of the 985A-to-G mutation in the medium-chain acyl-CoA dehydrogenase (MCAD) gene among Japanese patients with sudden infant death syndrome, Reye syndrome, unknown fatty acid oxidation disorders and severe motor and intellectual disabilities was studied using the PCR/Nco-I method for molecular diagnosis. A frequency study of this common mutation was also conducted on blood samples and left over Guthrie cards from 329 healthy newborns in Japan. Neither heterozygotes nor homozygotes for the 985A-to-G mutation were identified among both patients and controls. The result of the present study accord with previous reports that MCAD deficiency is a common disorder in Caucasians, but quite rare among Japanese. Therefore, newborn mass-screening for MCAD deficiency using this method will not be practical in Japan. However, it still seems necessary to investigate a child with fatty acid oxidation disorder for the presence of MCAD deficiency, using both biochemical and molecular genetic methods.
 ...
PMID:Frequency of 985A-to-G mutation in medium-chain acyl-CoA dehydrogenase gene among patients with sudden infant death syndrome, Reye syndrome, severe motor and intellectual disabilities and healthy newborns in Japan. 884 May 34

A clinical survey of Japanese patients with mitochondrial fatty acid beta-oxidation and related disorders (FAODs) was performed with questionnaires sent to 187 institutions, where inborn errors of metabolism could be managed in Japan, including a search of related literature published between 1985 and 2000. Sixty-four patients with ten types of FAODs were found. Carnitine palmitoyltransferase 2 deficiency and glutaric aciduria type 2 were most common (17 and 14 patients, respectively). As of 2000, there were no patients with medium-chain acyl-CoA dehydrogenase deficiency, which is common in Caucasians. Age at onset was under 2 years in 38 (59%) of the patients. Eight (13%) patients had neonatal onset. Twenty-one (55%) of the 38 children with an initial attack under 2 years of age had acute encephalopathy or a Reye syndrome-like illness. Half of the patients presented within 2 years of birth died or were handicapped. On the other hand, 19 (79%) of the 24 with onset after 2 years of age had muscle symptoms and 23 (96%) of the 24 grew and developed normally. Though the precise incidence of FAODs in Japan is still unknown, as a consequence of the development of diagnostic procedures the number of FAOD cases being diagnosed appears to have increased. Mass screening for FAODs during the neonatal period will greatly aid in prevention of attacks and related effects.
 ...
PMID:A survey of Japanese patients with mitochondrial fatty acid beta-oxidation and related disorders as detected from 1985 to 2000. 1242 13

The objective of the present study was to investigate the in vitro effects of octanoic acid, which accumulates in medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and in Reye syndrome, on key enzyme activities of energy metabolism in the cerebral cortex of young rats. The activities of the respiratory chain complexes I-IV, creatine kinase, and Na+,K(+)-ATPase were evaluated. Octanoic acid did not alter the electron transport chain and creatine kinase activities, but, in contrast, significantly inhibited Na+,K(+)-ATPase activity both in synaptic plasma membranes and in homogenates prepared from cerebral cortex. Furthermore, decanoic acid, which is also increased in MCAD deficiency, and oleic acid strongly reduced Na+,K(+)-ATPase activity, whereas palmitic acid had no effect. We also examined the effects of incubating glutathione and trolox (alpha-tocopherol) alone or with octanoic acid on Na+,K(+)-ATPase activity. Tested compounds did not affect Na+,K(+)-ATPase activity by itself, but prevented the inhibitory effect of octanoic acid. These results suggest that inhibition of Na+,K(+)-ATPase activity by octanoic acid is possibly mediated by oxidation of essential groups of the enzyme. Considering that Na+,K(+)-ATPase is critical for normal brain function, it is feasible that the significant inhibition of this enzyme activity by octanoate and also by decanoate may be related to the neurological dysfunction found in patients affected by MCAD deficiency and Reye syndrome.
 ...
PMID:Evidence that antioxidants prevent the inhibition of Na+,K(+)-ATPase activity induced by octanoic acid in rat cerebral cortex in vitro. 1289 42

Medium- and short-chain l-3-hydroxy-acyl-CoA dehydrogenase (M/SCHAD) deficiency is a recessively inherited disorder of fatty acid oxidation. Currently, only four patients from three families have been reported in the literature. All these patients presented with hypoglycemia associated with hyperinsulinism (HI). This association suggests that there is a role for M/SCHAD in regulating the pancreatic secretion of insulin. We present a fifth patient whose presentation was similar to Reye syndrome, a feature in common with most of the previously recognized disorders of fatty acid oxidation but with no clinical evidence of HI. Sequencing of the HAD1 gene on chromosome 4 revealed compound heterozygosity for two novel missense mutations, 170A>G, resulting in D45G, and 676T>C, resulting in Y214H. The mutant enzymes were expressed and subjected to kinetic analysis. Y214H has no detectable activity, whilst D45G, which resides in the cofactor-binding pocket, has an altered K(m) for NADH (96 microM versus 24 microM for the wild-type). This represents the first kinetic M/SCHAD mutant, which explains the high residual activity in skin fibroblasts. The lack of obvious HI in this patient may be related to the high residual activity and indicates that HI associated with M/SCHAD deficiency may only be present with complete deficiency. The spectrum of M/SCHAD phenotype should be broadened to include acute liver disease.
 ...
PMID:Reye-like syndrome resulting from novel missense mutations in mitochondrial medium- and short-chain l-3-hydroxy-acyl-CoA dehydrogenase. 1743 78

Accumulation of organic acids as well as their CoA and carnitine esters in tissues and body fluids is a common finding in organic acidurias, beta-oxidation defects, Reye syndrome, and Jamaican vomiting sickness. Pathomechanistic approaches for these disorders have been often focused on the effect of accumulating organic acids on mitochondrial energy metabolism, whereas little is known about the pathophysiologic role of short- and medium-chain acyl-CoAs and acylcarnitines. Therefore, we investigated the impact of short- and medium-chain organic acids, acylcarnitines, and acyl-CoAs on central components of mitochondrial energy metabolism, namely alpha-ketoglutarate dehydrogenase complex, pyruvate dehydrogenase complex, and single enzyme complexes I-V of respiratory chain. Although at varying degree, all acyl-CoAs had an inhibitory effect on pyruvate dehydrogenase complex and alpha-ketoglutarate dehydrogenase complex activity. Effect sizes were critically dependent on chain length and number of functional groups. Unexpectedly, octanoyl-CoA was shown to inhibit complex III. The inhibition was noncompetitive regarding reduced ubiquinone and uncompetitive regarding cytochrome c. In addition, octanoyl-CoA caused a blue shift in the gamma band of the absorption spectrum of reduced complex III. This effect may play a role in the pathogenesis of medium-chain and multiple acyl-CoA dehydrogenase deficiency, Reye syndrome, and Jamaican vomiting sickness which are inherited and acquired conditions of intracellular accumulation of octanoyl-CoA.
 ...
PMID:Impact of short- and medium-chain organic acids, acylcarnitines, and acyl-CoAs on mitochondrial energy metabolism. 1858 32

Reye syndrome is an acute metabolic encephalopathy, largely affecting children and adolescents. In Reye-like syndrome, because of inborn errors of metabolism, hypoglycemia, hypoketonemia, elevated ammonia, and organic aciduria are often evident. It is well-known that fatty-acid oxidation defects can present as Reye-like syndrome. The most commonly diagnosed metabolic disorder in association with Reye syndrome has been medium-chain acyl coenzyme A dehydrogenase deficiency. The present consensus seems to be that Reye syndrome is very rare, and that any child suspected of manifesting this disorder should undergo investigations for inborn errors of metabolism. We recently treated a child with "Reye-like illness" who possibly manifested a long-chain acyl dehydrogenase deficiency, and who had also ingested aspirin. We discuss the possible pathogenesis of the disorder in this child. The end results of mitochondrial dysfunction in Reye syndrome and Reye-like illness may be similar.
 ...
PMID:Reye syndrome and reye-like syndrome. 1872 66

Reye syndrome (RS) is an acute metabolic encephalopathy and hepatopathy affecting children and adolescents. Outbreaks of RS were common in United States until the early 1980s. However, after the abolition of salicylate (aspirin) therapy for infectious diseases such as influenza or varicella in patients under 18 years of age the incidence decreased. Now classical RS is rare and RS is considered a secondary mitochondrial disease. Reye-like syndrome (RLS), resulting from congenital errors of mitochondrial fatty oxidation, especially medium-chain acyl-CoA dehydrogenase deficiency, has increased due to progress in diagnostic techniques and methods after 1990. Diagnostic differentiation between RS and RLS is difficult because the end results of mitochondrial dysfunction in RS and RLS may be similar.
 ...
PMID:[Reye syndrome and Reye-like syndrome]. 2140 Aug 38

Complex I deficiency causes Leigh syndrome, fatal infant lactic acidosis, and neonatal cardiomyopathy. Mutations in more than 100 nuclear DNA and mitochondrial DNA genes miscode for complex I subunits or assembly factors. ACAD9 is an acyl-CoA dehydrogenase with a novel function in assembly of complex I; biallelic mutations cause progressive encephalomyopathy, recurrent Reye syndrome, and fatal cardiomyopathy. We describe the first autopsy in fatal neonatal lethal lactic acidosis due to mutations in ACAD9 that reduced complex I activity. We identified mitochondrial hyperplasia in cardiac myocytes, diaphragm muscle, and liver and renal tubules in formalin-fixed, paraffin-embedded tissue using immunohistochemistry for mitochondrial antigens. Whole-exome sequencing revealed compound heterozygous variants in the ACAD9 gene: c.187G>T (p.E63*) and c.941T>C (p.L314P). The nonsense mutation causes late infantile lethality; the missense variant is novel. Autopsy-derived fibroblasts had reduced complex I activity (53% of control) with normal activity in complexes II to IV, similar to reported cases of ACAD9 deficiency.
...
PMID:Neonatal multiorgan failure due to ACAD9 mutation and complex I deficiency with mitochondrial hyperplasia in liver, cardiac myocytes, skeletal muscle, and renal tubules. 2682 6

A boy aged 6 years and 3 months developed upper respiratory tract infection and pyrexia 2 months ago and was given oral administration of nimesulide by his parents according to directions. Half an hour later, the boy experienced convulsions and cardiopulmonary arrest, and emergency examination found hypoketotic hypoglycemia, metabolic acidosis, significant increases in serum aminotransferases and creatine kinase, and renal damage. Recovery of consciousness and vital signs was achieved after cardiopulmonary resuscitation, but severe mental and movement regression was observed. The boy had a significant reduction in free carnitine in blood and significant increases in medium- and long-chain fatty acyl carnitine, urinary glutaric acid, 3-hydroxy glutaric acid, isovalerylglycine, and ethylmalonic acid, suggesting the possibility of multiple acyl-CoA dehydrogenase deficiency. After the treatment with vitamin B2, L-carnitine, and bezafibrate, the boy gradually improved, and reexamination after 3 months showed normal biochemical parameters. The boy had compound heterozygous mutations in the ETFDH gene, i.e., a known mutation, c.341G>A (p.R114H), from his mother and a novel mutation, c.1484C>G (p.P495R), from his father. Finally, he was diagnosed with multiple acyl-CoA dehydrogenase deficiency. Reye syndrome and sudden death symptoms were caused by nimesulide-induced acute metabolic crisis. It is concluded that inherited metabolic diseases may be main causes of Reye syndrome and sudden death, and biochemical and genetic analyses are the key to identifying underlying diseases.
 ...
PMID:[Reye syndrome and sudden death symptoms after oral administration of nimesulide due to upper respiratory tract infection in a boy]. 3047 28


<< Previous 1 2 3