Successful reversal of propionic acidaemia associated cardiomyopathy: evidence for low myocardial coenzyme Q10 status and secondary mitochondrial dysfunction as an underlying pathophysiological mechanism

Mitochondrion. 2014 Jul:17:150-6. doi: 10.1016/j.mito.2014.07.001. Epub 2014 Jul 8.

Abstract

Dilated cardiomyopathy is a rare complication in propionic acidaemia (PA). Underlying pathophysiological mechanisms are poorly understood. We present a child of Pakistani consanguineous parents, diagnosed with late-onset PA at 18months of age. He presented a mild phenotype, showed no severe further decompensations, normal growth and psychomotor development on a low protein diet and carnitine supplementation. At 15years, a mildly dilated left ventricle was noticed. At 17years he presented after a 2-3month history of lethargy and weight loss with severe decompensated dilated cardiomyopathy. He was stabilised on inotropic support and continuous haemofiltration; a Berlin Heart biventricular assist device was implanted. He received d,l-hydroxybutyrate 200mg/kg/day, riboflavin and thiamine 200mg/day each and coenzyme Q10 (CoQ10). Myocardial biopsy showed endocardial fibrosis, enlarged mitochondria, with atypical cristae and slightly low respiratory chain (RC) complex IV activity relative to citrate synthase (0.012, reference range 0.014-0.034). Myocardial CoQ10 was markedly decreased (224pmol/mg, reference range 942-2738), with a marginally decreased white blood cell level (34pmol/mg reference range 37-133). The dose of CoQ10 was increased from 1.5 to 25mg/kg/day. Cardiomyopathy slowly improved allowing removal of the external mechanical cardiac support after 67days. We demonstrate for the first time low myocardial CoQ10 in cardiomyopathy in PA, highlighting secondary mitochondrial impairment as a relevant causative mechanism. According to these findings, a high-dose CoQ10 supplementation could be a potential adjuvant therapeutic to be considered in PA-related cardiomyopathy.

Keywords: Cardiomyopathy; Coenzyme Q10; Inborn metabolic disease; Propionic acidaemia; Respiratory chain; Ubiquinone.

Publication types

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

MeSH terms

  • Adolescent
  • Biopsy
  • Cardiomyopathies / complications*
  • Cardiomyopathies / drug therapy
  • Cardiomyopathies / pathology
  • Humans
  • Infant
  • Male
  • Mitochondria / chemistry*
  • Myocardium / pathology*
  • Propionic Acidemia / drug therapy*
  • Propionic Acidemia / physiopathology*
  • Treatment Outcome
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / analysis
  • Ubiquinone / therapeutic use
  • Vitamins / therapeutic use*

Substances

  • Vitamins
  • Ubiquinone
  • coenzyme Q10