Intermittent-relapsing pyruvate dehydrogenase complex deficiency: a case with clinical, biochemical, and neuroradiological reversibility

Dev Med Child Neurol. 2012 May;54(5):472-6. doi: 10.1111/j.1469-8749.2011.04151.x. Epub 2011 Dec 5.

Abstract

Pyruvate dehydrogenase complex (PDHC) deficiency causes encephalomyopathies, of which there are four major categories: (1) neonatal encephalopathy with lactic acidosis; (2) an early infantile form, which (3) at times resembles Leigh syndrome; and (4) a later-onset form. Long-term clinical and radiological follow-up is still incompletely elucidated. We report a 12-year-old male with intermittent-relapsing PDHC deficiency who presented with three typical acute episodes of metabolic decompensation over 7 years. Neuroimaging showed reversible signal abnormalities in the basal ganglia, inferior olivary nuclei, periaqueductal grey matter, and dentate nuclei, with evidence of lactate on magnetic resonance spectroscopy. Molecular analysis of PDH1A revealed a novel hemizygous c.1045G>A mutation, predicting a p.A349T missense mutation. He was treated with thiamine supplementation and, while on this regimen, he experienced several intercurrent febrile episodes without neurological compromise. This case report stresses the importance of performing neuroimaging during acute clinical episodes because brain lesions in PDHC deficiency may be transient and reversible, and false-negative results may mislead the diagnosis and delay the treatment.

Publication types

  • Case Reports

MeSH terms

  • Alleles
  • Brain / pathology
  • Child
  • DNA Mutational Analysis
  • Wirtschaft
  • Hemizygote
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy
  • Male
  • Mutation, Missense / genetics
  • Pyruvate Dehydrogenase (Lipoamide) / genetics*
  • Pyruvate Dehydrogenase Complex Deficiency Disease / diagnosis*
  • Pyruvate Dehydrogenase Complex Deficiency Disease / genetics
  • Pyruvate Dehydrogenase Complex Deficiency Disease / therapy
  • Recurrence
  • Thiamine / therapeutic use

Substances

  • Pyruvate Dehydrogenase (Lipoamide)
  • pyruvate dehydrogenase E1alpha subunit
  • Thiamine