title: Riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency with unknown genetic defect.
abstract: Multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare autosomal recessively inherited disorder of fatty acid metabolism due to ETFA, ETFB or ETFDH mutations. Riboflavin treatment ameliorates symptoms and metabolic profile in ETFDH-related MADD patients. We report on a 20-year-old boy with an 8-year history of progressive difficulty in walking, running and climbing stairs. Muscle biopsy showed a lipid myopathy and the acylcarnitine profile analysis was suggestive of MADD. Nevertheless, no evidence of molecular defects in the ETFA, ETFB and ETFDH exons or intron-exon boundaries was found. Treatment with riboflavin for 1 year resulted in a clear improvement in motor functions. Our report shows that some cases of MADD are not linked to ETFA, ETFB and ETFDH exon or intron-exon boundary changes. They could be due to quite rare promoter or deep intronic mutations or, most likely, to some unknown genetic defect. We therefore suggest to extend in these cases molecular studies to cDNA analysis and indicate the need of extensive pedigree studies to identify other possible disease-related loci. Most important, treatment of these cases with riboflavin can also be effective. Therefore, early diagnosis is essential to achieve the best treatment response.
authors.affiliation: Clinical Neurology, Section for Neuromuscular Diseaseas and Neuropathies, University Hospital "Spedali Civili", Pz.le Spedali Civili 1, 25100, Brescia, Italy.
authors.forename: Maria Sofia
authors.initials: MS
authors.lastname: Cotelli
authors.forename: Valentina
authors.initials: V
authors.lastname: Vielmi
authors.forename: Marco
authors.initials: M
authors.lastname: Rimoldi
authors.forename: Manuela
authors.initials: M
authors.lastname: Rizzetto
authors.forename: Barbara
authors.initials: B
authors.lastname: Castellotti
authors.forename: Valeria
authors.initials: V
authors.lastname: Bertasi
authors.forename: Alice
authors.initials: A
authors.lastname: Todeschini
authors.forename: Valeria
authors.initials: V
authors.lastname: Gregorelli
authors.forename: Carla
authors.initials: C
authors.lastname: Baronchelli
authors.forename: Cinzia
authors.initials: C
authors.lastname: Gellera
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Filosto
mesh_terms: D044927:Electron-Transferring Flavoproteins / Q000235:genetics; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000235:genetics; D008297:Male; D054069:Multiple Acyl Coenzyme A Dehydrogenase Deficiency / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics; D012256:Riboflavin / Q000627:therapeutic use*; D016896:Treatment Outcome; D014803:Vitamin B Complex / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D044927:Electron-Transferring Flavoproteins; D007506:Iron-Sulfur Proteins; D014803:Vitamin B Complex; D000587:Oxidoreductases Acting on CH-NH Group Donors; C023120:electron-transferring-flavoprotein dehydrogenase; D012256:Riboflavin