Beneficial effect of pyruvate therapy on Leigh syndrome due to a novel mutation in PDH E1α gene

Brain Dev. 2012 Feb;34(2):87-91. doi: 10.1016/j.braindev.2011.03.003. Epub 2011 Mar 31.

Abstract

Leigh syndrome (LS) is a progressive untreatable degenerating mitochondrial disorder caused by either mitochondrial or nuclear DNA mutations. A patient was a second child of unconsanguineous parents. On the third day of birth, he was transferred to neonatal intensive care units because of severe lactic acidosis. Since he was showing continuous lactic acidosis, the oral supplementation of dichloroacetate (DCA) was introduced on 31st day of birth at initial dose of 50 mg/kg, followed by maintenance dose of 25 mg/kg/every 12 h. The patient was diagnosed with LS due to a point mutation of an A-C at nucleotide 599 in exon 6 in the pyruvate dehydrogenase E1α gene, resulting in the substitution of aspartate for threonine at position 200 (N200T). Although the concentrations of lactate and pyruvate in blood were slightly decreased, his clinical conditions were deteriorating progressively. In order to overcome the mitochondrial or cytosolic energy crisis indicated by lactic acidosis as well as clinical symptoms, we terminated the DCA and administered 0.5 g/kg/day TID of sodium pyruvate orally. We analyzed the therapeutic effects of DCA or sodium pyruvate in the patient, and found that pyruvate therapy significantly decreased lactate, pyruvate and alanine levels, showed no adverse effects such as severe neuropathy seen in DCA, and had better clinical response on development and epilepsy. Though the efficacy of pyruvate on LS will be evaluated by randomized double-blind placebo-controlled study design in future, pyruvate therapy is a possible candidate for therapeutic choice for currently incurable mitochondrial disorders such as LS.

Publication types

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

MeSH terms

  • Alanine / blood
  • Cells, Cultured
  • Child, Preschool
  • Dichloroacetic Acid / therapeutic use*
  • Electroencephalography
  • Fibroblasts / enzymology
  • Humans
  • Lactic Acid / blood
  • Leigh Disease / drug therapy*
  • Leigh Disease / genetics*
  • Leigh Disease / physiopathology
  • Male
  • Mutation / genetics*
  • Pyruvate Dehydrogenase (Lipoamide) / genetics*
  • Pyruvic Acid / blood
  • Pyruvic Acid / cerebrospinal fluid
  • Pyruvic Acid / therapeutic use*
  • Statistics, Nonparametric

Substances

  • Lactic Acid
  • Pyruvic Acid
  • Dichloroacetic Acid
  • Pyruvate Dehydrogenase (Lipoamide)
  • pyruvate dehydrogenase E1alpha subunit
  • Alanine