Riboflavin-responsive lipid-storage myopathy caused by ETFDH gene mutations

Abstract

The research findings suggest that the majority of Chinese patients with RR-LSM are caused by a mild type of MADD with unique myopathy which is due to ETFDH gene mutation.

A case of late-onset riboflavin responsive multiple acyl-CoA dehydrogenase deficiency (MADD) with a novel mutation in ETFDH gene

“…To our knowledge, the former mutation has been reported with late onset riboflavin-responsive MADD in China [4]. The latter has not been previously reported.…”

A Case of Late Onset Riboflavin-responsive Multiple Acyl-CoA Dehydrogenase Deficiency Manifesting as Recurrent Rhabdomyolysis and Acute Renal Failure

“…The former mutation was reported in a Chinese female case, whose disease onset was at the age of 23 and only one heterozygous mutation was identified (12). This may be due to mutations in the promoter region, or the nonsense mediated decay pathway resulted from mutations such as exon deletions which cannot be identified by genomic sequencing (12). The latter mutation had not been described previously and the amino acid of this site is conserved among vertebrate, plant, and some insects and fungi.…”

“…Although the details of the electron transfer machinery within ETF-QO still remain uncertain, FAD and 4Fe4S are thought to work as cofactors and the equilibration between these two cofactors is indispensable for the proper transferring of electrons to ubiquinone. Interestingly, most of the known mutations in the ETFDH gene are associated with amino acid substitution in the region of the FAD or ubiquinone domains (2,12). We speculate that in the present case the former substitution influenced the affinity of FAD to ETF-QO, thereby impairing the electron transfer machinery in mitochondria, and compound heterozygous mutations including 4Fe4S cluster domain may have had some involvement with myocyte vulnerability, which may have led to rhabdomyolysis, but compound heterozygous mutations on such different domains most likely prevented the development of symptoms until the forties though biochemical analysis of the residual enzyme activity should be undertaken.…”

“…In agreement with previous reports, the present case harboring ETFDH mutations also showed good responses to riboflavin. Olsen et al suggested that a single amino acid substitution in the region of the protein that forms the interface between the FAD and ubiquinone binding domains would be responsible for the riboflavin responsiveness, whereas most nonresponders had a premature termination codon, which leads to nonsense-mediated decay of the transcript (2,12). Nevertheless, the clear mechanism of the genotype-riboflavinresponsiveness has not yet been established.…”

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

“…They estimated that the frequency of FAODs in Japan is at least 1/5,000 births, implying that the frequency of MADD is about 1/20,000. Some studies have investigated the epidemiology of MADD in southern China, where c.250G>A mutation in ETFDH is carried at high frequency in patients with riboflavin-responsive MADD (Law et al 2009;Liang et al 2009;Er et al 2010;Lan et al 2010;Wen et al 2010;Wang et al 2011).…”