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Pyruvate dehydrogenase deficiency presenting as intermittent isolated acute ataxia

F-G Debray1, M Lambert, R Gagne

  • 1Division of Medical Genetics, Department of Pediatrics, CHU Sainte-Justine, Université de Montreal, Montreal, Québec, Canada.

Neuropediatrics
|May 28, 2008
PubMed

Insights

Pyruvate dehydrogenase (PDH) deficiency can present with unusual intermittent neurological symptoms, even with normal lactate levels. Early recognition is crucial for managing this rare genetic disorder.

Area of Science:

  • Biochemistry
  • Genetics
  • Neurology

Background:

  • Pyruvate dehydrogenase (PDH) deficiency is a rare metabolic disorder affecting cellular energy production.
  • Unusual and intermittent clinical presentations can delay diagnosis.

Observation:

  • Two siblings with a novel PDHA1 gene mutation (G585C) exhibited recurrent isolated ataxia in infancy.
  • Symptoms initially resolved but progressed to severe encephalopathy, with death in their twenties.
  • Normal blood and CSF lactate levels were observed, and no thiamine responsiveness was noted.

Findings:

  • A new mutation (G585C) in the PDHA1 gene was identified as the cause of PDH deficiency.
  • The mutation, though in the thiamine pyrophosphate binding domain, did not result in thiamine responsiveness.
  • The study highlights a spectrum of intermittent neurological symptoms associated with PDH deficiency.

Implications:

  • PDH deficiency should be considered in the differential diagnosis of unexplained intermittent neurological symptoms.
  • The long-term prognosis for PDH deficiency remains uncertain and requires further investigation.
  • Normal CSF lactate levels do not exclude the diagnosis of PDH deficiency.
Abstract

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