Affinage

ETFDH

Electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial · UniProt Q16134

Length
617 aa
Mass
68.5 kDa
Annotated
2026-06-09
65 papers in source corpus 19 papers cited in narrative 19 extracted findings
Cross-family judge faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ETFDH encodes ETF-ubiquinone oxidoreductase (ETF-QO), a nuclear-encoded iron-sulfur flavoprotein of the inner mitochondrial membrane that channels electrons from electron-transfer flavoprotein into the respiratory chain by reducing ubiquinone, thereby linking fatty acid β-oxidation to mitochondrial bioenergetics (PMID:10444348, PMID:30709034). Catalysis proceeds by sequential electron transfer through a single [4Fe-4S] cluster and an FAD cofactor positioned ~18.6 Å apart, and reduction of the iron-sulfur cluster is obligatory for ubiquinone reductase activity: lowering its midpoint potential through mutation of cluster-proximal residues impairs both ubiquinone reduction and ETF semiquinone disproportionation (PMID:18069858, PMID:18037314). Pathogenic ETFDH mutations destabilize the protein and compromise FAD binding, with riboflavin acting as a pharmacological chaperone that post-translationally stabilizes variant ETF-QO by restoring FAD homeostasis rather than altering transcript levels (PMID:22611163, PMID:30232818, PMID:42216180). Defective ETF-QO uncouples β-oxidation from ATP synthesis, producing reactive oxygen species, lipid droplet accumulation, secondary CoQ10 deficiency, and activation of BCL-2/mitochondrial apoptotic signaling, the molecular basis of multiple acyl-CoA dehydrogenase deficiency (MADD/glutaric aciduria type II) (PMID:17412732, PMID:30709034, PMID:39455656). A substantial fraction of disease alleles act not as simple missense changes but by disrupting splicing — strengthening exonic silencers, causing exon skipping, or triggering nonsense-mediated decay — and unstable variants are additionally cleared through the ubiquitin-proteasome pathway (PMID:24123825, PMID:35314173, PMID:40075430).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1999 Medium

    Establishing that ETF-QO is a nuclear-encoded inner mitochondrial membrane protein and mapping its gene provided the genetic and subcellular framework for all subsequent disease and mechanistic work.

    Evidence FISH and somatic cell hybridization localizing ETFDH to chromosome 4q33

    PMID:10444348

    Open questions at the time
    • Did not address catalytic mechanism or cofactor content
    • No functional characterization of the protein
  2. 2007 High

    Quantifying the geometry of the two redox cofactors and demonstrating that iron-sulfur cluster reduction is required for catalysis defined the electron-transfer mechanism of ETF-QO.

    Evidence EPR relaxation-enhancement interspin distance measurement across three species plus site-directed mutagenesis with potentiometric and activity assays

    PMID:18037314 PMID:18069858

    Open questions at the time
    • Mutated residues are model probes, not necessarily disease alleles
    • Did not resolve how ETF docks and delivers electrons
  3. 2007 Medium

    Linking ETFDH mutations to secondary CoQ10 deficiency and riboflavin-responsive MADD connected enzyme dysfunction to defined clinical metabolic phenotypes and a treatment.

    Evidence Patient muscle biochemistry, respiratory chain and ETF-QO activity assays before/after riboflavin, with ETFDH sequencing

    PMID:17412732 PMID:17584774

    Open questions at the time
    • Mechanism of riboflavin responsiveness unresolved at this stage
    • Single-cohort/single-patient observations
  4. 2012 High

    Showing that RR-MADD variants are folding-defective and stabilized by FAD/riboflavin established a chaperone mechanism for riboflavin therapy and connected misfolding to ROS leakage.

    Evidence HEK-293 expression of variants with thermal stability, activity, Hsp60 co-IP, and cellular peroxide assays

    PMID:22611163

    Open questions at the time
    • Hsp60 association shown by co-IP without reciprocal/structural validation
    • Did not quantify FAD occupancy directly
  5. 2018 High

    Demonstrating in vivo that riboflavin raises variant ETF-QO protein in proportion to FAD but not mRNA confirmed FAD homeostasis as the post-translational basis of riboflavin rescue.

    Evidence Etfdh p.A84T knock-in mouse on high-fat/riboflavin-deficient diet with FAD measurement, Western blot, mRNA quantification, and patient fibroblast validation

    PMID:30232818

    Open questions at the time
    • Single mutation knock-in
    • Did not map FAD-binding kinetics of individual variants
  6. 2019 Medium

    Defining how ETF-QO mutations uncouple β-oxidation from bioenergetics and drive lipid accumulation clarified the downstream cellular pathology of MADD and the basis for CoQ10 supplementation.

    Evidence Patient lymphoblastoid cells with ATP synthesis, membrane potential, lipid droplet and peroxide assays plus riboflavin/CoQ10 rescue

    PMID:30709034

    Open questions at the time
    • Lymphoblastoid model not tissue-specific
    • Did not separate direct enzyme loss from secondary CoQ10 deficiency
  7. 2024 Medium

    Identifying activation of the BCL-2/MOMP apoptotic cascade in mutant-expressing neuronal cells linked ETF-QO dysfunction to a defined cell-death program reversible by CoQ10.

    Evidence NSC-34 expression model with Western blot for BAX/PUMA/cytochrome c/caspases, ROS and neurite assays with CoQ10 rescue

    PMID:27935074 PMID:39455656

    Open questions at the time
    • Overexpression model in a single neuronal line
    • Causal ordering of ROS, apoptosis, and metabolite toxicity not established
  8. 2022 Medium

    Characterizing splicing-disrupting and proteasome-degraded alleles revealed that ETFDH disease is frequently driven by transcript and protein turnover defects rather than missense catalytic loss alone.

    Evidence Minigene splice assays, RNA pull-down identifying hnRNP/SRSF regulators, RT-PCR, NMD analysis, and ubiquitin-proteasome assays identifying E3 ligases and a ubiquitination site

    PMID:24123825 PMID:32292771 PMID:35314173 PMID:40075430

    Open questions at the time
    • E3 ligase set identified in a single study without in vivo validation
    • ZNF267/polycystic kidney link is correlative
  9. 2026 Medium

    Structure-guided modeling of an in-frame FAD-domain deletion and in vivo Drosophila knock-in models connected specific structural lesions to FAD-binding loss, cardiac and muscle lipid pathology, and compensatory mitochondrial biogenesis.

    Evidence Patient iPSCs with minigene/RT-PCR and crystal-structure-based modeling; CRISPR Drosophila knock-ins with respirometry, lipid, ROS and energy-stress marker assays (one preprint)

    PMID:42216180 PMID:42239388

    Open questions at the time
    • Drosophila findings are a non-peer-reviewed preprint
    • Structural consequence of the deletion is modeled, not experimentally resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure of human ETF-QO in complex with ETF and ubiquinone, and a unified model relating individual variant cofactor occupancy to clinical riboflavin responsiveness, remain to be established.
  • No experimental human ETF-QO/ETF complex structure in the corpus
  • No systematic variant-by-variant FAD-occupancy/responsiveness map

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 2
Localization
GO:0005739 mitochondrion 2
Pathway
R-HSA-1430728 Metabolism 2 R-HSA-1643685 Disease 2
Partners
ETFHSP60STUB1

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 ETF-QO (ETFDH) contains a single [4Fe-4S]2+,1+ cluster and one equivalent of FAD. Site-directed mutagenesis of residues Y501 and T525 (equivalent to Y533 and T558 in porcine ETF-QO) near the iron-sulfur cluster demonstrated that these residues are within hydrogen-bonding distance of cysteine ligands. Single mutations Y501F and T525A decreased the midpoint potential of the iron-sulfur cluster from +37 mV (wild-type) to -60 mV, and the double mutant Y501F/T525A to -128 mV. Lowering the midpoint potential decreased steady-state ubiquinone reductase activity and ETF semiquinone disproportionation, demonstrating that reduction of the iron-sulfur cluster is required for catalytic activity. Site-directed mutagenesis, potentiometric titrations monitored by CW EPR, steady-state ubiquinone reductase activity assay Biochemistry High 18069858
2007 Electron spin relaxation enhancement measurements established that the point-dipole interspin distance between the [4Fe-4S]+ cluster and the FAD semiquinone in ETF-QO is 18.6 ± 1 Å in human, porcine, and Rhodobacter sphaeroides ETF-QO, consistent with the value calculated from the crystal structure of porcine ETF-QO, confirming proximity of the two redox cofactors within the enzyme. Electron spin relaxation enhancement (inversion recovery EPR) on redox-poised proteins; comparison with crystal structure distances Journal of magnetic resonance High 18037314
2007 Mutations in ETFDH cause a secondary deficiency of coenzyme Q10 (CoQ10) in skeletal muscle. Patients with ETFDH mutations showed severely decreased respiratory chain complex I and II+III activities and significantly reduced muscle CoQ10, establishing that ETFDH deficiency leads to secondary CoQ10 deficiency and that late-onset glutaric aciduria type II and myopathic CoQ10 deficiency are allelic disorders. Biochemical measurement of CoQ10 and respiratory chain complexes in muscle homogenates; ETFDH gene sequencing; tandem mass spectrometry Brain Medium 17412732
2007 Mutations in ETFDH (encoding ETF:QO) cause riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency (RR-MADD). In one patient, ETF:QO mutations were associated with riboflavin-sensitive impairment of ETF:QO activity, and partial deficiencies of flavin-dependent acyl-CoA dehydrogenases and respiratory chain complexes were restored to control levels after riboflavin treatment, indicating that FAD cofactor availability modulates ETF:QO function. ETF:QO enzyme activity assay before and after riboflavin treatment; biochemical analysis of acyl-CoA dehydrogenase and respiratory chain complex activities; ETFDH sequencing Brain Medium 17584774
2012 Riboflavin responsiveness in MADD patients with ETF-QO variants is mechanistically explained by a chaperone effect of FAD/riboflavin on variant ETF-QO folding. Variant ETF-QO proteins associated with RR-MADD showed milder folding defects correctable by riboflavin, while non-responsive variants caused severe misfolding. Variant ETF-QO proteins showed prolonged association with the Hsp60 chaperonin in the mitochondrial matrix, and increased cellular peroxide production, indicating that structurally defective ETF-QO leaks electrons and generates reactive oxygen species. HEK-293 cell expression system; steady-state protein level analysis; ETF-QO activity assay; thermal stability measurements; cellular peroxide production assay; Hsp60 co-immunoprecipitation Human molecular genetics High 22611163
2013 The ETFDH c.158A>G variant causes exon skipping rather than a missense substitution. RNA pull-down of nuclear proteins showed that the variant increases the strength of a preexisting exonic splicing silencer (ESS) motif UAGGGA, which binds inhibitory hnRNP A1, hnRNP A2/B1, and hnRNP H proteins, preventing binding of positive splicing regulators SRSF1 and SRSF5 to overlapping exonic splicing enhancer elements, thereby causing exon 2 skipping and ETFDH protein degradation. Splicing reporter minigenes; RNA pull-down with nuclear proteins; patient sample mRNA analysis; protein identification of binding partners Human mutation High 24123825
2018 FAD homeostasis disturbance is a crucial pathomechanism of RR-MADD. In Etfdh knock-in mice (carrying the p.A84T mutation) subjected to high-fat, riboflavin-deficient diet, both ETF:QO protein and FAD concentrations were significantly decreased in tissues. After riboflavin treatment, ETF:QO protein increased in proportion to elevated FAD concentrations but not to mRNA levels, demonstrating that riboflavin stabilizes variant ETF:QO protein post-translationally by rebuilding FAD homeostasis. Etfdh knock-in mouse model; FAD concentration measurements; Western blot; mRNA quantification; patient fibroblast validation Annals of neurology High 30232818
1999 ETF-QO (ETFDH gene product) is a nuclear-encoded protein located in the inner mitochondrial membrane. The ETF-QO gene was mapped to human chromosome 4q33 by somatic cell hybridization and fluorescence in situ hybridization. Fluorescence in situ hybridization (FISH); somatic cell hybridization Molecular genetics and metabolism Medium 10444348
2019 ETFDH c.250G>A and c.92C>T mutations in ETF-QO uncouple fatty acid β-oxidation from mitochondrial bioenergetics, resulting in decreased ATP synthesis, dissipated mitochondrial membrane potentials, reduced mitochondrial bioenergetics, and increased neutral lipid droplets and lipid peroxides in MADD patient-derived lymphoblastoid cells. Riboflavin and/or coenzyme Q10 supplementation rescued cells from lipid droplet accumulation. Patient-derived lymphoblastoid cells; ATP synthesis assay; mitochondrial membrane potential measurement; lipid droplet quantification; lipid peroxide assay; pharmacological rescue with riboflavin/CoQ10 Cells Medium 30709034
2017 ETFDH p.Ala84Thr mutation increases ROS production and causes neurite shortening in cells expressing the mutant protein. Suberic acid (an accumulated intermediate metabolite in MADD) significantly impairs neurite outgrowth of NSC34 cells. Supplementation with carnitine, riboflavin, or CoQ10 restores neurite length, suggesting that ETF-QO dysfunction causes neuronal defects mediated by metabolic intermediates and oxidative stress. Cell expression system (ETFDH wild-type vs. mutant); ROS production assay; neurite length measurement; pharmacological rescue Muscle & nerve Medium 27935074
2022 A novel ETFDH c.725C>T (p.T242I) mutation enhances degradation of ETF-QO via the ubiquitin proteasome pathway. Five E3 ubiquitin ligases (STUB1, RNF40, UBE3C, CUL3, and CUL1) and one ubiquitin modification site (Cysteine C101) on ETF-QO were identified. Molecular analysis of ETFDH variant; ubiquitin proteasome pathway assay; identification of E3 ligases and ubiquitination site Clinica chimica acta Medium 35314173
2024 ETFDH p.Ala84Thr mutation activates the BCL-2/mitochondrial outer membrane permeabilization/apoptosis pathway in NSC-34 cells, as shown by elevated levels of BAX, PUMA, cytochrome c, caspase-3, and caspase-9. CoQ10 treatment downregulated these proapoptotic proteins and mitigated neurite growth defects. NSC-34 cell expression model; Western blot for BCL-2 family proteins; cytochrome c and caspase activity measurement; neurite length assay; pharmacological rescue with CoQ10 Scientific reports Medium 39455656
2013 Elevated muscle CoQ10 in riboflavin-responsive MADD patients with ETFDH mutations is not due to primary CoQ10 biosynthesis dysregulation but rather secondary to mitochondrial mass proliferation. When CoQ10 levels were normalized to citrate synthase (a mitochondrial mass marker), there was no significant difference from controls. Increased mitochondrial DNA copy number confirmed mitochondrial proliferation. PPARα and lipid metabolism genes were upregulated. HPLC measurement of CoQ10 in muscle; citrate synthase normalization; mitochondrial DNA copy number quantification; CoQ10 biosynthesis gene expression analysis; PPARα expression Molecular genetics and metabolism Medium 23628458
2020 ETFDH c.579A>G, a synonymous variant, causes exon 5 skipping. Transcript analysis in vivo and minigene splice assay in vitro confirmed that this synonymous change disrupts normal ETFDH mRNA splicing, leading to production of a truncated protein. In vivo transcript analysis; in vitro minigene splice assay; RT-PCR Frontiers in pediatrics Medium 32292771
2025 ETFDH c.487+2T>A mutation leads to mRNA degradation through nonsense-mediated decay (NMD), confirmed by minigene splice assay and RT-PCR. Downregulation of ETFDH in cell experiments led to lipid accumulation, enhanced oxidative stress, and upregulation of ZNF267 expression, suggesting ETFDH is a key regulatory gene in lipid homeostasis and potentially in polycystic kidney development. Minigene splice assay; RT-PCR; in vitro cell knockdown experiments; lipid accumulation assay; oxidative stress measurement; ZNF267 expression analysis Orphanet journal of rare diseases Medium 40075430
2026 ETFDH c.1049G>A causes predominant exon 9 skipping resulting in an in-frame 48-amino acid deletion within the FAD-binding domain, confirmed by patient-derived iPSCs and minigene assays. Structural modeling based on the human ETFDH crystal structure showed this deletion disrupts the stabilizing interaction between Arg364 and Glu246, predicting compromised FAD binding. Western blot showed markedly reduced ETFDH protein levels (<10%) in patient cells. iPSC-derived patient cells; minigene splice assay; RT-PCR; structural modeling based on crystal structure; Western blot Orphanet journal of rare diseases Medium 42216180
2018 A splice site ETFDH mutation (c.1285+1G>A, intron 10) alters ETFDH RNA splicing as confirmed by RT-PCR, leading to production of a truncated protein. In silico structural analysis showed the associated missense mutation (c.560C>T) causes instability and loss of protein activation, while the splice variant induces a dramatic conformational change. Patients with at least one missense mutation in the FAD-binding domain may respond to riboflavin or carnitine due to recovery of some enzymatic activity. RT-PCR for splicing analysis; in silico 3D structural prediction of ETF-QO Lipids in health and disease Low 30424791
2026 In Drosophila CRISPR knock-in models carrying patient-relevant Etf-QO missense mutations in FAD- and ubiquinone-binding domains, defective Etf-QO activity disrupts electron flow, promotes ROS production, impairs fatty acid β-oxidation, causes lipid droplet accumulation in skeletal muscle and cardiac tissue, reduces mitochondrial oxygen consumption, and leads to metabolic cardiomyopathy. Activation of AMPK, PGC-1α, and Tfam indicates compensatory mitochondrial biogenesis in response to energy stress. CRISPR/Cas9 Drosophila knock-in models; locomotor assays; cardiac functional analysis; lipid droplet quantification; in vivo respirometry; ROS measurement; ATP quantification; Western blot for energy stress markers bioRxivpreprint Medium 42239388
2024 ETFDH downregulation in cancer cells (NALM-6 acute lymphoblastic leukemia) limits flexibility of OXPHOS fuel utilization but paradoxically increases cancer cell bioenergetics and accelerates neoplastic growth by activation of the mTORC1/BCL-6/4E-BP1 signaling axis. ETFDH knockdown/knockout in cancer cell lines; bioenergetic profiling; mTORC1/BCL-6/4E-BP1 signaling pathway analysis bioRxivpreprint Low bio_10.1101_2024.10.25.620155

Source papers

Stage 0 corpus · 65 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 The myopathic form of coenzyme Q10 deficiency is caused by mutations in the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene. Brain : a journal of neurology 242 17412732
2007 ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency. Brain : a journal of neurology 240 17584774
2003 Clear relationship between ETF/ETFDH genotype and phenotype in patients with multiple acyl-CoA dehydrogenation deficiency. Human mutation 191 12815589
2009 ETFDH mutations, CoQ10 levels, and respiratory chain activities in patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency. Neuromuscular disorders : NMD 114 19249206
2009 Riboflavin-responsive lipid-storage myopathy caused by ETFDH gene mutations. Journal of neurology, neurosurgery, and psychiatry 92 19758981
2011 Molecular analysis of 51 unrelated pedigrees with late-onset multiple acyl-CoA dehydrogenation deficiency (MADD) in southern China confirmed the most common ETFDH mutation and high carrier frequency of c.250G>A. Journal of molecular medicine (Berlin, Germany) 81 21347544
2012 Molecular mechanisms of riboflavin responsiveness in patients with ETF-QO variations and multiple acyl-CoA dehydrogenation deficiency. Human molecular genetics 78 22611163
2013 Clinical features and ETFDH mutation spectrum in a cohort of 90 Chinese patients with late-onset multiple acyl-CoA dehydrogenase deficiency. Journal of inherited metabolic disease 76 24357026
2010 High frequency of ETFDH c.250G>A mutation in Taiwanese patients with late-onset lipid storage myopathy. Clinical genetics 52 20370797
2009 Novel mutations in ETFDH gene in Chinese patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency. Clinica chimica acta; international journal of clinical chemistry 44 19265687
2010 High resolution melting analysis facilitates mutation screening of ETFDH gene: applications in riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency. Clinica chimica acta; international journal of clinical chemistry 35 20138856
2017 Heterogeneous Phenotypes in Lipid Storage Myopathy Due to ETFDH Gene Mutations. JIMD reports 33 28456887
2018 Characterization of two ETFDH mutations in a novel case of riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency. Lipids in health and disease 32 30424791
2007 Impact of mutations on the midpoint potential of the [4Fe-4S]+1,+2 cluster and on catalytic activity in electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO). Biochemistry 32 18069858
2004 Lipid-storage myopathy and respiratory insufficiency due to ETFQO mutations in a patient with late-onset multiple acyl-CoA dehydrogenation deficiency. Journal of inherited metabolic disease 31 15669683
2018 ETFDH Mutations and Flavin Adenine Dinucleotide Homeostasis Disturbance Are Essential for Developing Riboflavin-Responsive Multiple Acyl-Coenzyme A Dehydrogenation Deficiency. Annals of neurology 29 30232818
2016 Significant clinical heterogeneity with similar ETFDH genotype in three Chinese patients with late-onset multiple acyl-CoA dehydrogenase deficiency. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 29 27000805
2013 The ETFDH c.158A>G variation disrupts the balanced interplay of ESE- and ESS-binding proteins thereby causing missplicing and multiple Acyl-CoA dehydrogenation deficiency. Human mutation 28 24123825
2011 Computational analysis of a novel mutation in ETFDH gene highlights its long-range effects on the FAD-binding motif. BMC structural biology 27 22013910
2013 Increased muscle coenzyme Q10 in riboflavin responsive MADD with ETFDH gene mutations due to secondary mitochondrial proliferation. Molecular genetics and metabolism 26 23628458
2019 Late-onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (MADD): case reports and epidemiology of ETFDH gene mutations. BMC neurology 24 31852447
2018 Novel ETFDH mutations in four cases of riboflavin responsive multiple acyl-CoA dehydrogenase deficiency. Molecular genetics and metabolism reports 24 29988809
2015 A case of late-onset riboflavin responsive multiple acyl-CoA dehydrogenase deficiency (MADD) with a novel mutation in ETFDH gene. Journal of the neurological sciences 21 25913573
2018 Patient with multiple acyl-CoA dehydrogenase deficiency disease and ETFDH mutations benefits from riboflavin therapy: a case report. BMC medical genomics 18 29615056
2017 A novel mutation in ETFDH manifesting as severe neonatal-onset multiple acyl-CoA dehydrogenase deficiency. Journal of the neurological sciences 18 29249369
2019 ETF-QO Mutants Uncoupled Fatty Acid β-Oxidation and Mitochondrial Bioenergetics Leading to Lipid Pathology. Cells 17 30709034
2014 Novel ETFDH mutation and imaging findings in an adult with glutaric aciduria type II. Muscle & nerve 17 23893693
2019 Expression and significance of ETFDH in hepatocellular carcinoma. Pathology, research and practice 14 31704152
2020 A novel electron transfer flavoprotein dehydrogenase (ETFDH) gene mutation identified in a newborn with glutaric acidemia type II: a case report of a Chinese family. BMC medical genetics 13 32393189
2007 Electron spin relaxation enhancement measurements of interspin distances in human, porcine, and Rhodobacter electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO). Journal of magnetic resonance (San Diego, Calif. : 1997) 13 18037314
2020 Neonatal-onset multiple acyl-CoA dehydrogenase deficiency (MADD) in the ETFDH gene: A case report and a literature review. Medicine 11 32925727
2019 Rhabdomyolysis and respiratory insufficiency due to the common ETFDH mutation of c.250G>A in two patients with late-onset multiple acyl-CoA dehydrogenase deficiency. Chinese medical journal 11 31058673
2017 Neurite growth could be impaired by ETFDH mutation but restored by mitochondrial cofactors. Muscle & nerve 11 27935074
2011 Multiple acyl-CoA-dehydrogenase deficiency (MADD)--a novel mutation of electron-transferring-flavoprotein dehydrogenase ETFDH. Journal of the neurological sciences 11 21616504
2024 A comparative study on riboflavin responsive multiple acyl-CoA dehydrogenation deficiency due to variants in FLAD1 and ETFDH gene. Journal of human genetics 8 38228875
2020 Correlation between ETFDH mutations and dysregulation of serum myomiRs in MADD patients. European journal of translational myology 7 32499892
2020 A Synonymous Variant c.579A>G in the ETFDH Gene Caused Exon Skipping in a Patient With Late-Onset Multiple Acyl-CoA Dehydrogenase Deficiency: A Case Report. Frontiers in pediatrics 6 32292771
2020 Clinical characteristics and gene mutation analysis of an adult patient with ETFDH‑related multiple acyl‑CoA dehydrogenase deficiency. Molecular medicine reports 6 33000234
2018 Long-term outcomes of a patient with late-onset multiple acyl-CoA dehydrogenase deficiency caused by novel mutations in ETFDH: A case report. Medicine 6 30508893
2017 A novel ETFDH mutation in an adult patient with late-onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency. The International journal of neuroscience 6 28914566
2022 Novel variant of ETFDH leading to multiple acyl-CoA dehydrogenase deficiency by promoting protein degradation via ubiquitin proteasome pathway. Clinica chimica acta; international journal of clinical chemistry 5 35314173
2021 Characterization of ETFDH and PHGDH Mutations in a Patient with Mild Glutaric Aciduria Type II and Serine Deficiency. Genes 5 34066864
2021 Clinical Presentations and Genetic Characteristics of Late-Onset MADD Due to ETFDH Mutations in Five Patients: A Case Series. Frontiers in neurology 4 34819910
2018 [A novel mutation in the ETFDH gene of an infant with multiple acyl-CoA dehydrogenase deficiency]. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 4 30022752
1999 Assignment of electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) to human chromosome 4q33 by fluorescence in situ hybridization and somatic cell hybridization. Molecular genetics and metabolism 4 10444348
2024 Deep Intronic ETFDH Variants Represent a Recurrent Pathogenic Event in Multiple Acyl-CoA Dehydrogenase Deficiency. International journal of molecular sciences 3 39273584
2020 Skin damage in a patient with lipid storage myopathy with a novel ETFDH mutation responsive to riboflavin. The International journal of neuroscience 3 32064983
2020 Late-onset MADD in Yemen caused by a novel ETFDH mutation misdiagnosed as ADEM. Multiple sclerosis and related disorders 3 33383363
2017 [Clinical features and ETFDH mutations of children with late-onset glutaric aciduria type II: a report of two cases]. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 3 28899466
2025 The difference of variation types between late-onset multiple acyl-CoA dehydrogenase deficiency patients carrying biallelic and single heterozygous variations in ETFDH: a systematic review and meta-analysis. Orphanet journal of rare diseases 2 40533849
2023 Case report: A novel c.1842_1845dup mutation of ETFDH in two Chinese siblings with multiple acyl-CoA dehydrogenase deficiency. Frontiers in pediatrics 2 36683804
2023 Case report: Novel ETFDH compound heterozygous mutations identified in a patient with late-onset glutaric aciduria type II. Frontiers in neurology 2 36779069
2022 A fatal case of neonatal onset multiple acyl-CoA dehydrogenase deficiency caused by novel mutation of ETFDH gene: case report. Italian journal of pediatrics 2 36064718
2022 Lipid storage myopathy due to late-onset multiple Acyl-CoA dehydrogenase deficiency with novel mutations in ETFDH: A case report. Frontiers in neurology 2 36588907
2017 Anesthetic management of a pediatric patient with Electron Transfer Flavoprotein Dehydrogenase deficiency (ETFDH) and acute appendicitis: case report and review of the literature. BMC anesthesiology 2 28851284
2024 ETFDH mutation involves excessive apoptosis and neurite outgrowth defect via Bcl2 pathway. Scientific reports 1 39455656
2019 [Analysis of ETFDH gene variation in a Chinese family affected with lipid storage myopathy]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 1 31598946
2026 Splicing defect and functional characterization of the ETFDH c.1049G > A VUS underlying transient MADD: an iPSC and minigene study. Orphanet journal of rare diseases 0 42216180
2026 Genotype-environment interaction drives the onset of riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency in carriers of single heterozygous ETFDH variants. Cell communication and signaling : CCS 0 42231330
2026 Exercise based Intervention For Metabolic Inflexibility Linked With Lipid Storage Myopathy Using Innovative CRISPR Etf-QO Mutant Knock-in Models. bioRxiv : the preprint server for biology 0 42239388
2025 A novel ETFDH mutation identified in a patient with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency. Intractable & rare diseases research 0 40046021
2025 Identification of ETFDH gene c. 487 + 2 T > A pathogenic variant and mechanisms for polycystic kidney in neonatal onset MADD. Orphanet journal of rare diseases 0 40075430
2024 A compound heterozygote case of glutaric aciduria type II in a patient carrying a novel candidate variant in ETFDH gene: A case report and literature review on compound heterozygote cases. Molecular genetics & genomic medicine 0 38967380
2024 Fatal multiple acyl-CoA dehydrogenase deficiency caused by ETFDH gene mutation: A case report. World journal of clinical cases 0 39156098
2022 Generation of a human induced pluripotent stem cell line (LZUSHi002-A) from a MADD patient with ETFDH mutation. Stem cell research 0 36162333

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