Successful treatment of infantile-onset ACAD9-related cardiomyopathy with a combination of sodium pyruvate, beta-blocker, and coenzyme Q10

J Pediatr Endocrinol Metab. 2019 Oct 25;32(10):1181-1185. doi: 10.1515/jpem-2019-0205.

Abstract

Mitochondrial acyl-CoA dehydrogenase 9 (ACAD9) deficiency is one of the common causes of respiratory chain complex I deficiency, which is characterized by cardiomyopathy, lactic acidemia, and muscle weakness. Infantile cardiomyopathy is the most common phenotype and is usually lethal by the age of 5 years. Riboflavin treatment is known to be effective in ~65% of the patients; however, the remaining are unresponsive to riboflavin and are in need of additional treatment measures. In this report, we describe a patient with ACAD9 deficiency who developed progressive cardiomyopathy at 8 months of age. As the patient's left ventricular ejection fraction (LVEF) kept decreasing to 45.4% at 1 year 8 months, sodium pyruvate treatment was introduced together with a beta-blocker and coenzyme Q10. This resulted in a steady improvement, with full and sustained normalization of cardiac function without riboflavin. The therapy, therefore, might be a useful addition for the treatment of ACAD9 deficiency.

Keywords: ACAD9; cardiomyopathy; deficiency; mitochondria; pyruvate; treatment.

Publication types

  • Case Reports

MeSH terms

  • Acidosis / complications
  • Acidosis / drug therapy*
  • Acidosis / pathology
  • Acyl-CoA Dehydrogenase / deficiency*
  • Acyl-CoA Dehydrogenases / deficiency*
  • Adrenergic beta-Antagonists / administration & dosage
  • Amino Acid Metabolism, Inborn Errors / complications
  • Amino Acid Metabolism, Inborn Errors / drug therapy*
  • Amino Acid Metabolism, Inborn Errors / pathology
  • Cardiomyopathies / complications
  • Cardiomyopathies / drug therapy*
  • Cardiomyopathies / pathology
  • Cardiomyopathy, Hypertrophic / complications
  • Cardiomyopathy, Hypertrophic / drug therapy*
  • Cardiomyopathy, Hypertrophic / pathology
  • Carvedilol / administration & dosage*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Infant, Newborn
  • Mitochondrial Diseases / complications
  • Mitochondrial Diseases / drug therapy*
  • Mitochondrial Diseases / pathology
  • Muscle Weakness / complications
  • Muscle Weakness / drug therapy*
  • Muscle Weakness / pathology
  • Prognosis
  • Pyruvates / administration & dosage*
  • Ubiquinone / administration & dosage
  • Ubiquinone / analogs & derivatives*
  • Vitamins / administration & dosage

Substances

  • Adrenergic beta-Antagonists
  • Pyruvates
  • Vitamins
  • Carvedilol
  • Ubiquinone
  • Acyl-CoA Dehydrogenases
  • Acyl-CoA Dehydrogenase
  • ACAD9 protein, human
  • coenzyme Q10

Supplementary concepts

  • Acyl-CoA Dehydrogenase Family, Member 9, Deficiency of