ETFDH mutations, CoQ10 levels, and respiratory chain activities in patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency

@article{Liang2009ETFDH,
  title={
 ETFDH mutations, CoQ10 levels, and respiratory chain activities in patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency},
  author={Wen-Chen Liang and Aya Ohkuma and Yukiko K. Hayashi and Luis C. L{\'o}pez and Michio Hirano and Ikuya Nonaka and Satoru Noguchi and Liang-Hui Chen and Yuh-Jyh Jong and Ichizo Nishino},
  journal={Neuromuscular Disorders},
  year={2009},
  volume={19},
  pages={212-216}
}

Figures and Tables from this paper

Molecular mechanisms of riboflavin responsiveness in patients with ETF-QO variations and multiple acyl-CoA dehydrogenation deficiency.

The results showed that variant ETF-QO proteins associated with non- and partially responsive MADD caused severe misfolding of ETF-ZO variant proteins when cultured in media with supplemented concentrations of riboflavin, and decreased thermal stability of the variants showed that FAD does not completely correct the structural defects induced by the variation.

Secondary coenzyme Q10 deficiency and oxidative stress in cultured fibroblasts from patients with riboflavin responsive multiple Acyl-CoA dehydrogenation deficiency.

It is shown that moderately decreased CoQ10 levels in fibroblasts from six unrelated RR-MADD patients were associated with increased levels of mitochondrial reactive oxygen species (ROS), suggesting that molecular oxygen can get access to the electrons in the misfolded ETF-QO protein, thereby generating superoxide and oxidative stress, which can be reversed by CoQ 10 treatment.

Multiple Acyl-CoA Dehydrogenation Deficiency (Glutaric Aciduria Type II) with a Novel Mutation of Electron Transfer Flavoprotein-Dehydrogenase in a Cat.

The affected animal presented with symptoms characteristic of MADD including hypoglycemia, hyperammonemia, vomiting, diagnostic organic aciduria, and accumulation of medium- and long-chain fatty acids in plasma and treatment with riboflavin and L-carnitine ameliorated the symptoms.

Riboflavin‐responsive multiple acyl‐CoA dehydrogenase deficiency: A frequent condition in the southern Chinese population

High‐dose riboflavin supplementation therapy has been shown to be efficacious in MADD patients with certain ETFDH mutations, including p.Ala84Thr, suggesting that MADD in most southern Chinese patients might be treatable.

Patient with multiple acyl-CoA dehydrogenase deficiency disease and ETFDH mutations benefits from riboflavin therapy: a case report

The findings support the role of WES as an effective tool in the diagnosis of highly heterogeneous disease and this has important implications in the therapeutic strategy of LSM treatment.

Riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency with unknown genetic defect

It is shown that some cases of MADD are not linked to ETFA, ETFB and ETFDH exon or intron–exon boundary changes, which could be due to quite rare promoter or deep intronic mutations or, most likely, to some unknown genetic defect.

Title Patient with multiple acyl-CoA dehydrogenase deficiency disease and ETFDH mutations benefits from riboflavin therapy : a case report

The findings support the role of WES as an effective tool in the diagnosis of highly heterogeneous disease and this has important implications in the therapeutic strategy of LSM treatment.

ETF dehydrogenase advances in molecular genetics and impact on treatment

The clinical features correlated with ETF-QO deficiency and the benefits obtained from different treatments, such as riboflavin, L-carnitine and/or coenzyme Q10 supplementation, and a diet poor in fat and protein are outlined.
...

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ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency.

This is the largest collection of riboflavin-responsive MADD patients ever reported, and the first demonstration of the molecular genetic basis for the disorder.

The myopathic form of coenzyme Q10 deficiency is caused by mutations in the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene.

The results indicate that the late-onset form of GAII and the myopathic form of CoQ10 deficiency are allelic diseases, and it is suggested to give patients both CoQ 10 and riboflavin supplementation, especially for long-term treatment.

Clear relationship between ETF/ETFDH genotype and phenotype in patients with multiple acyl‐CoA dehydrogenation deficiency

Interestingly, the data suggest that homozygosity for two null mutations causes fetal development of congenital anomalies resulting in a type I disease phenotype, indicating that the effect of the ETF/ETFDH genotype in patients with milder forms of MADD, in whom residual enzyme activity allows modulation of the enzymatic phenotype, may be influenced by environmental factors like cellular temperature.

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It is postulate that defective maintenance of mitochondrial FAD levels explains this patient's riboflavin-responsive multiple acyl-CoA dehydrogenation disorder phenotype.

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Late‐onset riboflavin‐responsive myopathy with combined multiple acyl coenzyme A dehydrogenase and respiratory chain deficiency

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Riboflavin therapy. Biochemical heterogeneity in two adult lipid storage myopathies.

Plasma acyl-carnitine and urinary organic acid profiles indicated multiple acyl coenzyme A dehydrogenase deficiency, which was mild in patient 1 and severe in patient 2, and biochemical parameters were either totally or partly corrected after riboflavin therapy.