title: Riboflavin-Responsive Multiple Acyl-CoA Dehydrogenase Deficiency Associated with Hepatoencephalomyopathy and White Matter Signal Abnormalities on Brain MRI.
abstract: Multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare inborn error of metabolism affecting both fatty acid and amino acid oxidation. It can manifest at any age, but riboflavin-responsiveness has mainly been described in less severely affected patients. We describe an infant with severe MADD presenting with profound hypotonia and hepatomegaly. Treatment with riboflavin improved his muscle strength, liver size, and biochemical markers. A homozygous mutation of electron transfer flavoprotein dehydrogenase (ETFDH) was found. His motor skills continued to progress until a fatal infection-triggered deterioration at the age of 34 months. We show changes in brain magnetic resonance imaging over the course of the disease, with profound white matter abnormalities during the deterioration phase. Aggregates of mitochondria with abnormal cristae in muscle electron microscopy were noticed already in infancy. An unusual lactate dehydrogenase (LDH) isoenzyme pattern with LDH-1 predominance was additionally observed. This case demonstrates riboflavin-responsiveness in a severely affected infant with both muscular and extramuscular involvement and further underlines the variable nature of this disease.
authors.affiliation: PEDEGO Research Unit, Department of Children and Adolescents, Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Vieira
authors.affiliation: PEDEGO Research Unit, Department of Clinical Genetics, Northern Finland Laboratory Centre (NordLab), Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Myllynen
authors.affiliation: Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland.
authors.forename: Marja
authors.initials: M
authors.lastname: Perhomaa
authors.affiliation: Department of Pathology, Oulu University Hospital, University of Oulu, Oulu, Finland.
authors.forename: Hannu
authors.initials: H
authors.lastname: Tuominen
authors.affiliation: PEDEGO Research Unit, Department of Clinical Genetics, Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland.
authors.forename: Riikka
authors.initials: R
authors.lastname: Keski-Filppula
authors.affiliation: Department of Clinical Neurophysiology, Oulu University Hospital, Oulu, Finland.
authors.forename: Seppo
authors.initials: S
authors.lastname: Rytky
authors.affiliation: PEDEGO Research Unit, Department of Clinical Genetics, Northern Finland Laboratory Centre (NordLab), Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland.
authors.forename: Leila
authors.initials: L
authors.lastname: Risteli
authors.affiliation: PEDEGO Research Unit, Department of Children and Adolescents, Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland.|Biocenter Oulu, University of Oulu, Oulu, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Uusimaa
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects; D006501:Hepatic Encephalopathy / Q000150:complications* / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D054069:Multiple Acyl Coenzyme A Dehydrogenase Deficiency / Q000150:complications* / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000503:physiopathology; D012256:Riboflavin / Q000627:therapeutic use*; D014803:Vitamin B Complex / Q000627:therapeutic use*; D066127:White Matter / Q000000981:diagnostic imaging / Q000187:drug effects
chemical_list: D014803:Vitamin B Complex; D012256:Riboflavin