EC Number   |
General Information |
Reference |
|---|
   1.1.1.211 | malfunction |
a patient with hemophagocytic lymphohistiocytosis and LCHAD deficiency suffers pancytopenia, liver failure, and rhabdomyolysis. LCHAD deficiency, especially in 1 to 6 months old infants with laboratory findings of hypoglycemia, metabolic acidosis, and elevated creatine kinase, may also have hemophagocytic lymphohistiocytosis (HLH), a secondary HLH may develop in patients with LCHAD deficiency |
740890 |
| 1.1.1.211 | malfunction |
analysis of the effects of the major long-chain monocarboxylic 3-hydroxylated fatty acids (LCHFA) accumulating in the disorders mitochondrial trifunctional protein (MTP) and long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) deficiencies, namely 3-hydroxytetradecanoic (3HTA) and 3-hydroxypalmitic (3HPA) acids, on important mitochondrial functions in rat skeletal muscle mitochondria 3HTA and 3HPA markedly increases resting and decrease ADP-stimulated and CCCP-stimulated (uncoupled) respiration. 3HPA provokes similar effects in permeabilized skeletal muscle fibers, validating the results obtained in purified mitochondria. 3HTA and 3HPA markedly diminish mitochondrial membrane potential, NAD(P)H content, and Ca2+ retention capacity in Ca2+-loaded mitochondria. Mitochondrial permeability transition (mPT) induction probably underlies these effects since they are totally prevented by cyclosporin A and ADP. In contrast, the dicarboxylic analogue of 3HTA does not alter the tested parameters. 3HTA and 3HPA behave as metabolic inhibitors, uncouplers of oxidative phosphorylation and mPT inducers in skeletal muscle. The pathomechanisms disrupting mitochondrial homeostasis may be involved in the muscle alterations characteristic ofMTP and LCHAD deficiencies |
-, 741457 |
| 1.1.1.211 | malfunction |
children with long-chain 3-hydroxyacyl-CoA dehydrogenasedeficiency (LCHAD) have a defect in the degradation of long-chain fatty acids and are at risk of hypoketotic hypoglycemia and insufficient energy production as well as accumulation of toxic fatty acid intermediates. lipolysis and accumulation of long chain acylcarnitines occurs before hypoglycemia in fasting children with LCHAD, which may indicate more limited fasting tolerance than previously suggested, phenotypes, overview. Early and increased lipolysis and accumulation of long chain acylcarnitines after 4 h of fasting, albeit no patients developed hypoglycemia |
740832 |
| 1.1.1.211 | malfunction |
defects in long-chain 3-hydroxy acyl-CoA dehydrogenase lead to hepatocellular carcinoma |
761287 |
| 1.1.1.211 | malfunction |
effects of long-chain 3-hydroxylated fatty acids (LCHFA) that accumulate in LCHAD deficiency on liver bioenergetics in mitochondrial preparations from young rats: 3-hydroxytetradecanoic (3HTA) and 3-hydroxypalmitic (3HPA) acids, the monocarboxylic acids that are found at the highest tissue concentrations in this disorder, act as metabolic inhibitors and uncouplers of oxidative phosphorylation. These fatty acids decrease ADP-stimulated and uncoupled respiration, mitochondrial membrane potential and NAD(P)H content, and, in contrast, increased resting respiration. 3HTA and 3HPA markedly reduce Ca2+ retention capacity and induce swelling in C2+-loaded mitochondria. The effects are mediated by mitochondrial permeability transition (MPT) induction since they are totally prevented by the classical MPT inhibitors cyclosporin A and ADP, as well as by ruthenium red, a Ca2+ uptake blocker. Long-chain monocarboxylic 3-hydroxylated fatty acids alter oxygen consumption in liver mitochondria. The major monocarboxylic LCHFA accumulating in LCHAD deficiency disrupt energy mitochondrial homeostasis in the liver leading to liver dysfunction |
-, 740106 |
| 1.1.1.211 | malfunction |
enzyme exon 15 deletion is embryonic lethal to the homozygous mice whereas heterozygous mice develop significant hepatic steatosis starting at young age (3 months old) and hepatocellular carcinoma at older age (more than13 months old) without any evidence of fibrosis or cirrhosis |
761287 |
| 1.1.1.211 | malfunction |
long-chain 3-hydroxy fatty acids accumulating in long-chain 3-hydroxyacyl-CoA dehydrogenase and mitochondrial trifunctional protein deficiencies uncouple oxidative phosphorylation in heart mitochondria. Cardiomyopathy is a common clinical feature of some inherited disorders of mitochondrial fatty acid beta-oxidation including mitochondrial trifunctional protein (MTP) and isolated long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiencies. 3-Hydroxytetradecanoic (3HTA) and 3-hydroxypalmitic (3HPA) acids increase resting respiration and diminish the respiratory control and ADP/O ratios using glutamate/malate or succinate as substrates. 3-hydroxydodecanoic (3HDDA), 3HTA and 3HPA decrease DELTAPsi, the matrix NAD(P)H pool, and hydrogen peroxide production. These fatty acids behave as uncouplers of oxidative phosphorylation. 3HTA-induced uncoupling-effect is not mediated by the adenine nucleotide translocator and that this fatty acid induced the mitochondrial permeability transition pore opening in calcium-loaded organelles since cyclosporin A prevents the reduction of mitochondrial DELTAPsi and swelling provoked by 3HTA |
-, 740641 |
| 1.1.1.211 | malfunction |
long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and trifunctional protein (TFP) deficiency are accompanied by increased levels of 3-hydroxypalmitoleoyl-carnitine combined with other hydroxylated long chain acylcarnitines, analysis of acylcarnitine profile of two LCHADD patients, overview. Patients with propionic acidemia (PA) or methylmalonic acidemia (MMA) also show high levels of 3-hydroxypalmitoleoyl-carnitine and heptadecanoylcarnitine |
740331 |
| 1.1.1.211 | malfunction |
long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency is characterized by lethargy, hypoglycemia, hypotonia, cardiomyopathy, and acute metabolic crisis |
761165 |
| 1.1.1.211 | malfunction |
long-chain 3-hydroxyacyl-CoA dehydrogenase, LCHAD, deficiency is a defect of the TFP complex caused by a mutation in the HADHA gene on short arm of chromosome 2 (2p23). The most common mutation (1528G.C, G510Q) is responsible for at least one allele in 60100 percent of individuals with LCHAD deficiency. LCHAD and TFP deficiencies are caused by different genetic mutations in the same protein, mitochondrial trifunctional protein (MTFP). Long-chain fatty acids are broken down by the MTFP after initial metabolism by very long-chain acyl-CoA dehydrogenase. In individuals with LCHAD deficiency, there is one enzymatic defect (3-hydroxylacyl-CoA dehydrogenase) which results in accumulation of long-chain hydroxylacylcarnitines. In TFP deficiency, the process of the b-oxidation includes defects in three enzymes, enoyl-CoA hydratase, 3-hydroxyl-CoA dehydrogenase (LCHAD), and 3-ketothiolase, which results in accumulation of mixed, long-chain acylcarnitine species. Although disorders of trifunctional protein (TFP) complex including longchain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and mitochondrial TFP deficiencies are extremely rare, the combined incidence of mitochondrial fatty acid disorders is quite frequent. With the expansion of newborn screening, what were once considered uncommon disorders are being identified with increasing frequency in asymptomatic infants. Infants with inborn errors of metabolism can present with breathing difficulties, acidosis (or alkalosis), and hypoglycemia, phenotype, detailed overview |
741064 |
