140094 20240504120052.0 10.1186/s13023-018-0784-8 doi pmid:30025539 pmid pmc:PMC6053715 pmc altmetric:45551002 altmetric DZNE-2020-06416 English 610 Repp, Birgit M 0 Clinical, biochemical and genetic spectrum of 70 patients with ACAD9 deficiency: is riboflavin supplementation effective? London 2018 BioMed Central online Crossref Springer Science and Business Media LLC 2018-07-19 print Crossref Springer Science and Business Media LLC 2018-12-01 article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1714743284_33 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Mitochondrial acyl-CoA dehydrogenase family member 9 (ACAD9) is essential for the assembly of mitochondrial respiratory chain complex I. Disease causing biallelic variants in ACAD9 have been reported in individuals presenting with lactic acidosis and cardiomyopathy.We describe the genetic, clinical and biochemical findings in a cohort of 70 patients, of whom 29 previously unpublished. We found 34 known and 18 previously unreported variants in ACAD9. No patients harbored biallelic loss of function mutations, indicating that this combination is unlikely to be compatible with life. Causal pathogenic variants were distributed throughout the entire gene, and there was no obvious genotype-phenotype correlation. Most of the patients presented in the first year of life. For this subgroup the survival was poor (50% not surviving the first 2 years) comparing to patients with a later presentation (more than 90% surviving 10 years). The most common clinical findings were cardiomyopathy (85%), muscular weakness (75%) and exercise intolerance (72%). Interestingly, severe intellectual deficits were only reported in one patient and severe developmental delays in four patients. More than 70% of the patients were able to perform the same activities of daily living when compared to peers.Our data show that riboflavin treatment improves complex I activity in the majority of patient-derived fibroblasts tested. This effect was also reported for most of the treated patients and is mirrored in the survival data. In the patient group with disease-onset below 1 year of age, we observed a statistically-significant better survival for patients treated with riboflavin. 899H - Addenda (POF3-899H) G:(DE-HGF)POF3-899H POF3-899H POF III 0 2018-07-19 Crossref http://creativecommons.org/licenses/by/4.0/ Dataset connected to CrossRef, PubMed, Acyl-CoA Dehydrogenase EC 1.3.8.7 NLM Chemicals Electron Transport Complex I EC 7.1.1.2 NLM Chemicals Riboflavin TLM2976OFR NLM Chemicals Acidosis: genetics MeSH Acidosis: metabolism MeSH Acidosis: pathology MeSH Activities of Daily Living MeSH Acyl-CoA Dehydrogenase: deficiency MeSH Acyl-CoA Dehydrogenase: genetics MeSH Acyl-CoA Dehydrogenase: metabolism MeSH Amino Acid Metabolism, Inborn Errors: genetics MeSH Amino Acid Metabolism, Inborn Errors: metabolism MeSH Amino Acid Metabolism, Inborn Errors: pathology MeSH Cardiomyopathy, Hypertrophic: genetics MeSH Cardiomyopathy, Hypertrophic: metabolism MeSH Cardiomyopathy, Hypertrophic: pathology MeSH Electron Transport Complex I: metabolism MeSH Female MeSH Humans MeSH Male MeSH Mitochondrial Diseases: genetics MeSH Mitochondrial Diseases: metabolism MeSH Mitochondrial Diseases: pathology MeSH Muscle Weakness: drug therapy MeSH Muscle Weakness: genetics MeSH Muscle Weakness: metabolism MeSH Muscle Weakness: pathology MeSH Prognosis MeSH Riboflavin: therapeutic use MeSH Mastantuono, Elisa 1 Alston, Charlotte L 2 Schiff, Manuel 3 Haack, Tobias B 4 Rötig, Agnes 5 Ardissone, Anna 6 Lombès, Anne 7 Catarino, Claudia B 8 Diodato, Daria 9 Schottmann, Gudrun 10 Poulton, Joanna 11 Burlina, Alberto 12 Jonckheere, An 13 Munnich, Arnold 14 Rolinski, Boris 15 Ghezzi, Daniele 16 Rokicki, Dariusz 17 Wellesley, Diana 18 Martinelli, Diego 19 Wenhong, Ding 20 Lamantea, Eleonora 21 Ostergaard, Elsebet 22 Pronicka, Ewa 23 Pierre, Germaine 24 Smeets, Hubert J M 25 Wittig, Ilka 26 Scurr, Ingrid 27 de Coo, Irenaeus F M 28 Moroni, Isabella 29 Smet, Joél 30 Mayr, Johannes A 31 Dai, Lifang 32 de Meirleir, Linda 33 Schuelke, Markus 34 Zeviani, Massimo 35 Morscher, Raphael J 36 McFarland, Robert 37 Seneca, Sara 38 Klopstock, Thomas P:(DE-2719)2810704 39 dzne Meitinger, Thomas P:(DE-HGF)0 40 Wieland, Thomas 41 Strom, Tim M 42 Herberg, Ulrike 43 Ahting, Uwe 44 Sperl, Wolfgang 45 Nassogne, Marie-Cecile 46 Ling, Han 47 Fang, Fang 48 Freisinger, Peter 49 Van Coster, Rudy 50 Strecker, Valentina 51 Taylor, Robert W 52 Häberle, Johannes 53 Vockley, Jerry 54 Prokisch, Holger 55 Wortmann, Saskia P:(DE-HGF)0 56 Corresponding author 10.1186/s13023-018-0784-8 : Springer Science and Business Media LLC, 2018-07-19 1 120 journal-article Crossref Orphanet Journal of Rare Diseases 13 2018 1750-1172 10.1186/s13023-018-0784-8 Vol. 13, no. 1, p. 120 PERI:(DE-600)2225857-7 1 13:1<120 120 Orphanet journal of rare diseases 13 2018 1750-1172 OpenAccess http://pub.dzne.de/record/140094/files/DZNE-2020-06416.pdf OpenAccess pdfa http://pub.dzne.de/record/140094/files/DZNE-2020-06416.pdf?subformat=pdfa Pubmed Central 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