Patient with multiple acyl-CoA dehydrogenation deficiency disease and FLAD1 mutations benefits from riboflavin therapy

M Auranen; A Paetau; P Piirilä; A Pohju; T Salmi; A Lamminen; M Löfberg; S Mosegaard; R K Olsen; T Tyni

doi:10.1016/j.nmd.2017.03.003

Patient with multiple acyl-CoA dehydrogenation deficiency disease and FLAD1 mutations benefits from riboflavin therapy

Neuromuscul Disord. 2017 Jun;27(6):581-584. doi: 10.1016/j.nmd.2017.03.003. Epub 2017 Mar 9.

Authors

M Auranen¹, A Paetau², P Piirilä³, A Pohju⁴, T Salmi⁵, A Lamminen⁶, M Löfberg⁷, S Mosegaard⁸, R K Olsen⁸, T Tyni⁹

Affiliations

¹ Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital, Finland. Electronic address: [email protected].
² Department of Pathology, HUSLAB, University of Helsinki and Helsinki University Hospital, Finland.
³ Unit of Clinical Physiology, HUS Medical Imaging Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
⁴ Clinical Nutrition Unit, Helsinki University Hospital, Finland.
⁵ Department of Clinical Neurophysiology, Medical Imaging Center, Helsinki University Hospital, Finland.
⁶ Department of Radiology, Medical Imaging Center, Helsinki University Hospital, Finland.
⁷ Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital, Finland.
⁸ Research Unit for Molecular Medicine, Department of Clinical Medicine, Health, Aarhus University Hospital and Aarhus University, Denmark.
⁹ Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Department of Pediatric Neurology, Hospital for Children and Adolescence, Helsinki University Central Hospital, Helsinki, Finland.

PMID: 28433476
DOI: 10.1016/j.nmd.2017.03.003

Abstract

Multiple acyl-CoA dehydrogenation deficiency is genetically heterogenous metabolic disease with mutations in genes involved in electron transfer to the mitochondrial respiratory chain. Disease symptoms vary from severe neonatal form to late-onset presentation with metabolic acidosis, lethargy, vomiting, muscle pain and weakness. Riboflavin therapy has been shown to ameliorate diseases symptoms in some of these patients. Recently, mutations in FAD synthase have been described to cause multiple acyl-CoA dehydrogenation deficiency. We describe here the effect of riboflavin supplementation therapy in a previously reported adult patient with multiple acyl-CoA dehydrogenation deficiency having compound heterozygous gene variations in FLAD1 (MIM: 610595) encoding FAD synthase. We present thorough clinical history including laboratory investigations, muscle MRI, muscle biopsy and spiroergometric analyses comprising of a follow-up of 20 years. Our data suggest that patients with adult-onset multiple acyl-CoA dehydrogenation deficiency with FLAD1 gene mutations also benefit from long-term riboflavin therapy.

Keywords: Genetics; Metabolic disease; Muscle disease; Neuromuscular disease.

Publication types

Case Reports

MeSH terms

Adult
Female
Frameshift Mutation*
Heterozygote
Humans
Multiple Acyl Coenzyme A Dehydrogenase Deficiency / diet therapy*
Multiple Acyl Coenzyme A Dehydrogenase Deficiency / genetics*
Multiple Acyl Coenzyme A Dehydrogenase Deficiency / pathology
Muscle, Skeletal
Mutation, Missense*
Riboflavin / therapeutic use*
Treatment Outcome

Substances

Riboflavin