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Mouse Models of Periventricular Leukomalacia
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Mouse Models of Periventricular Leukomalacia

Published on: May 18, 2010

Unilateral periventricular leukomalacia in association with pyruvate dehydrogenase deficiency

Ruchi Sharma1, Mark J Sharrard, Daniel J Connolly

  • 1Department of Paediatric Neurology, Sheffield Children's Hospital, Sheffield, UK.

Developmental Medicine and Child Neurology
|September 8, 2011
PubMed

Insights

Pyruvate dehydrogenase (PDH) deficiency, a cause of lactic acidosis, can present with unique brain imaging findings. This case highlights unilateral periventricular leukomalacia (PVL) in a patient with PDH E1 alpha deficiency.

Area of Science:

  • Biochemistry
  • Neurology
  • Genetics

Background:

  • Pyruvate dehydrogenase (PDH) deficiency is a significant inherited metabolic disorder.
  • It is a primary cause of congenital lactic acidosis and neurological impairment in infants.
  • Deficiency in the PDH E1 alpha subunit is a common cause of this condition.

Purpose of the Study:

  • To report a case of PDH deficiency in an infant presenting with neurological dysfunction.
  • To describe an unusual neuroradiological finding associated with PDH deficiency.
  • To emphasize the importance of considering PDH deficiency in specific clinical contexts.

Main Methods:

  • Clinical case presentation of a female infant.
  • Biochemical analysis of plasma and cerebrospinal fluid lactate and pyruvate.
  • Neuroimaging via magnetic resonance imaging (MRI) of the brain.
  • Biopsy of skin fibroblasts for PDH deficiency assay and mutation analysis of the E1 alpha subunit.

Main Results:

  • The infant presented with failure to thrive, microcephaly, hypertonia, and global developmental delay.
  • Elevated plasma and CSF lactate with normal lactate-pyruvate ratio were observed.
  • MRI revealed unilateral periventricular leukomalacia (PVL) with subependymal cyst, a previously undescribed feature in PDH deficiency.
  • Genetic analysis confirmed PDH E1 alpha subunit deficiency.

Conclusions:

  • PDH deficiency should be considered in the differential diagnosis of infantile lactic acidosis and neurological impairment.
  • Unilateral PVL, particularly with atypical perinatal history, may suggest PDH deficiency.
  • Early diagnosis and management, including ketogenic diet and dichloroacetate, are crucial.

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