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Biochemical investigations revealed acylcarnitine and organic acid profiles resembling those seen in MADD, that is, multiple acyl\u2010CoA dehydrogenase deficiencies (OMIM #231680) a rare inherited disorder of fatty acids, amino acids, and choline metabolism. The patient carried a single pathogenetic variant in the <jats:italic>ETFDH<\/jats:italic> gene (c.524G&gt;A, p.Arg175His) and no pathogenetic variant in the riboflavin (Rf) homeostasis related genes (<jats:italic>SLC52A1<\/jats:italic>, <jats:italic>SLC52A2<\/jats:italic>, <jats:italic>SLC52A3<\/jats:italic>, <jats:italic>SLC25A32<\/jats:italic>, <jats:italic>FLAD1<\/jats:italic>). Instead, compound heterozygosity was found in the <jats:italic>ACAD8<\/jats:italic> gene (c.512C&gt;G, p.Ser171Cys; c.822C&gt;A, p.Asn274Lys), coding for isobutyryl\u2010CoA dehydrogenase (IBD), whose pathogenic variants are associated to IBD deficiency (OMIM #611283), a rare autosomal recessive disorder of valine catabolism. The c.822C&gt;A was never previously described in a patient. Subsequent further analyses of Rf homeostasis showed reduced levels of flavins in plasma and altered FAD\u2010dependent enzymatic activities in erythrocytes, as well as a significant reduction in the level of the plasma membrane Rf transporter 2 in erythrocytes. The observed Rf\/flavin scarcity in this patient, possibly associated with a decreased ETF:QO efficiency might be responsible for the observed MADD\u2010like phenotype. The patient's clinical picture improved after supplementation of Rf, <jats:sc>l<\/jats:sc>\u2010carnitine, Coenzyme Q10, and also 3OH\u2010butyrate. This report demonstrates that, even in the absence of genetic defects in genes involved in Rf homeostasis, further targeted molecular analysis may reveal secondary and possibly treatable biochemical alterations in this pattern.<\/jats:p>","DOI":"10.1002\/jmd2.12292","type":"journal-article","created":{"date-parts":[[2022,5,7]],"date-time":"2022-05-07T08:42:41Z","timestamp":1651912961000},"page":"276-291","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Combined <scp>isobutyryl\u2010CoA<\/scp> and multiple <scp>acyl\u2010CoA<\/scp> dehydrogenase deficiency in a boy with altered riboflavin homeostasis"],"prefix":"10.1002","volume":"63","author":[{"given":"Albina","family":"Tummolo","sequence":"first","affiliation":[{"name":"Metabolic Diseases and Clinical Genetics Unit Children's Hospital \u201cGiovanni XXIII\u201d  Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piero","family":"Leone","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnology and Biopharmaceutics University of Bari \u201cA. Moro\u201d  Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Tolomeo","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnology and Biopharmaceutics University of Bari \u201cA. Moro\u201d  Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita","family":"Solito","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnology and Biopharmaceutics University of Bari \u201cA. Moro\u201d  Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Mattiuzzo","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children Hospital  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca Romana","family":"Lepri","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children Hospital  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tania","family":"Lor\u00e8","sequence":"additional","affiliation":[{"name":"Regional Centre for Neonatal Screening Children's Hospital \u201cGiovanni XXIII\u201d  Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Cardinali","sequence":"additional","affiliation":[{"name":"Regional Centre for Neonatal Screening Children's Hospital \u201cGiovanni XXIII\u201d  Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donatella","family":"De Giovanni","sequence":"additional","affiliation":[{"name":"Metabolic Diseases and Clinical Genetics Unit Children's Hospital \u201cGiovanni XXIII\u201d  Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simonetta","family":"Simonetti","sequence":"additional","affiliation":[{"name":"Regional Centre for Neonatal Screening Children's Hospital \u201cGiovanni XXIII\u201d  Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Barile","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnology and Biopharmaceutics University of Bari \u201cA. 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