2. Academic Validation
  3. Evidence of a wide spectrum of cardiac involvement due to ACAD9 mutations: Report on nine patients

Evidence of a wide spectrum of cardiac involvement due to ACAD9 mutations: Report on nine patients

  • Mol Genet Metab. 2016 Jul;118(3):185-189. doi: 10.1016/j.ymgme.2016.05.005.
Joseph P Dewulf 1,  Catherine Barrea 2,  Marie-Françoise Vincent 1,  Corinne De Laet 3,  Rudy Van Coster 4,  Sara Seneca 5,  Sandrine Marie 1,  Marie-Cécile Nassogne 6
Affiliations

Affiliations

  • 1 Université Catholique de Louvain, Cliniques Universitaires Saint-Luc, Service de Biochimie génétique, B-1200 Brussels, Belgium.
  • 2 Université Catholique de Louvain, Cliniques Universitaires Saint-Luc, Service de Cardiologie Pédiatrique, B-1200 Brussels, Belgium.
  • 3 Nutrition and Metabolism Unit, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, Brussels, Belgium.
  • 4 Pediatric Neurology, University Hospital, De Pintelaan 185, B-9000 Gent, Belgium.
  • 5 Center for Medical Genetics, UZ Brussel, Research Group for Reproduction and Genetics (VUB), Laarbeeklaan 101, B-1090 Brussels, Belgium.
  • 6 Université Catholique de Louvain, Cliniques Universitaires Saint-Luc, Service de Neurologie pédiatrique, B-1200 Brussels, Belgium. Electronic address: Marie-cecile.nassogne@uclouvain.be.
PMID: 27233227 DOI: 10.1016/j.ymgme.2016.05.005
Abstract

Acyl-CoA dehydrogenase 9 (ACAD9) is a mitochondrial protein involved in Oxidative Phosphorylation complex I biogenesis. This protein also exhibits acyl-CoA dehydrogenase (ACAD) activity. ACAD9-mutated patients have been reported to suffer from primarily heart, muscle, liver, and nervous system disorders. ACAD9 mutation is suspected in cases of elevated lactic acid levels combined with complex I deficiency, and confirmed by ACAD9 gene analysis. At least 18 ACAD9-mutated patients have previously been reported, usually displaying severe cardiac involvement. We retrospectively studied nine additional patients from three unrelated families with a wide spectrum of cardiac involvement between the families as well as the patients from the same families. All patients exhibited elevated lactate levels. Deleterious ACAD9 mutations were identified in all patients except one for whom it was not possible to recover DNA. To our knowledge, this is one of the first reports on isolated mild ventricular hypertrophy due to ACAD9 mutation in a family with moderate symptoms during adolescence. This report also confirms that dilated cardiomyopathy may occur in conjunction with ACAD9 mutation and that some patients may respond clinically to riboflavin treatment. Of note, several patients suffered from patent ductus arteriosus (PDA), with one exhibiting a complex congenital heart defect. It is yet unknown whether these cardiac manifestations were related to ACAD9 mutation. In conclusion, this disorder should be suspected in the presence of lactic acidosis, complex I deficiency, and any cardiac involvement, even mild.

Keywords

ACAD9; Acyl-COA dehydrogenase 9; Cardiomyopathy; Complex I deficiency.

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