Optic neuropathy linked to ACAD9 pathogenic variants: A potentially riboflavin-responsive disorder?


Journal

Mitochondrion
ISSN: 1872-8278
Titre abrégé: Mitochondrion
Pays: Netherlands
ID NLM: 100968751

Informations de publication

Date de publication:
07 2021
Historique:
received: 06 04 2021
revised: 19 05 2021
accepted: 19 05 2021
pubmed: 24 5 2021
medline: 27 1 2022
entrez: 23 5 2021
Statut: ppublish

Résumé

Mitochondrial complex I (CI) deficiencies (OMIM 252010) are the commonest inherited mitochondrial disorders in children. Acyl-CoA dehydrogenase 9 (ACAD9) is a flavoenzyme involved chiefly in CI assembly and possibly in fatty acid oxidation. Biallelic pathogenic variants result in CI dysfunction, with a phenotype ranging from early onset and sometimes fatal mitochondrial encephalopathy with lactic acidosis to late-onset exercise intolerance. Cardiomyopathy is often associated. We report a patient with childhood-onset optic and peripheral neuropathy without cardiac involvement, related to CI deficiency. Genetic analysis revealed compound heterozygous pathogenic variants in ACAD9, expanding the clinical spectrum associated to ACAD9 mutations. Importantly, riboflavin treatment (15 mg/kg/day) improved long-distance visual acuity and demonstrated significant rescue of CI activity in vitro.

Identifiants

pubmed: 34023438
pii: S1567-7249(21)00073-8
doi: 10.1016/j.mito.2021.05.002
pii:
doi:

Substances chimiques

Acyl-CoA Dehydrogenases EC 1.3.-
ACAD9 protein, human EC 1.3.99.-
Riboflavin TLM2976OFR

Types de publication

Case Reports Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

169-174

Informations de copyright

Copyright © 2021 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Auteurs

Naig Gueguen (N)

Department of Biochemistry and Molecular Biology, CHU Angers, 49933 Angers, France; University of Angers, Unité Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique (CNRS) 6015, Institut National de la Santé et de la Recherche Médicale (INSERM) U1083, 49933 Angers, France.

Julie Piarroux (J)

CHU Montpellier, Département de Neuropédiatrie, Montpellier, France.

Emmanuelle Sarzi (E)

NeuroMyoGene Institute-UCBL/CNRS UMR5310/INSERM U1217-Lyon, France.

Mehdi Benkirane (M)

PhyMedExp, CNRS, INSERM, University of Montpellier, Montpellier, France; Laboratoire de Génétique Moléculaire, Institut Universitaire de Recherche Clinique, CHU de Montpellier, France.

Gael Manes (G)

INM, University Montpellier, INSERM, Montpellier, France.

Cécile Delettre (C)

INM, University Montpellier, INSERM, Montpellier, France.

Pascal Amedro (P)

PhyMedExp, CNRS, INSERM, University of Montpellier, Montpellier, France; Pediatric and Adult Congenital Cardiology Department, M3C Rare Cardiac Disease Reference Center, CHU Montpellier, France.

Nicolas Leboucq (N)

Département de Neuroradiologie, CHU Montpellier, Montpellier, France.

Michel Koenig (M)

PhyMedExp, CNRS, INSERM, University of Montpellier, Montpellier, France; Laboratoire de Génétique Moléculaire, Institut Universitaire de Recherche Clinique, CHU de Montpellier, France.

Pierre Meyer (P)

CHU Montpellier, Département de Neuropédiatrie, Montpellier, France; PhyMedExp, CNRS, INSERM, University of Montpellier, Montpellier, France.

Isabelle Meunier (I)

National Center in Rare Diseases, Genetics of Sensory Diseases, University Hospital, Montpellier, France.

Pascal Reynier (P)

Department of Biochemistry and Molecular Biology, CHU Angers, 49933 Angers, France; University of Angers, Unité Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique (CNRS) 6015, Institut National de la Santé et de la Recherche Médicale (INSERM) U1083, 49933 Angers, France.

Guy Lenaers (G)

University of Angers, Unité Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique (CNRS) 6015, Institut National de la Santé et de la Recherche Médicale (INSERM) U1083, 49933 Angers, France.

Agathe Roubertie (A)

CHU Montpellier, Département de Neuropédiatrie, Montpellier, France; INM, University Montpellier, INSERM, Montpellier, France; National Center in Rare Diseases, Genetics of Sensory Diseases, University Hospital, Montpellier, France. Electronic address: a-roubertie@chu-montpellier.fr.

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Classifications MeSH