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Pyruvate Dehydrogenase Complex Deficiencies

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Mitochondrial Disorders Caused by Nuclear Genes

Abstract

Pyruvate dehydrogenase complex (PDC) deficiencies, affecting a critical step in carbohydrate oxidative metabolism, have heterogeneous genetic causes and outcomes. There are few correlations between numerous mutations, affecting at least 10 genes, measured PDC enzyme activity, and the clinical outcome. The presentation varies by age and sex. Symptoms may include lactic acidosis, frequently severe in neonates, and neurological manifestations, which include developmental delay/intellectual disability, hypotonia, hypertonia, dystonia, seizures, ataxia, and axonal neuropathy. Neuroimaging frequently reveals grey and white matter abnormalities, including ventriculomegaly, abnormalities of the corpus callosum, and/or Leigh syndrome. Defects that are not specific to PDC are more likely to have additional systemic features. Mortality is greater in males, and diminishes after early childhood. Biochemical, immunohistochemical, and/or genetic testing may be necessary to suggest or confirm a diagnosis. Treatment options include use of ketogenic diets, thiamine supplementation, and, less commonly, dichloroacetate, for which case reports suggest variable benefits. Gene therapy remains a potential future treatment for PDC deficiency.

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Authors and Affiliations

  1. Pediatric Endocrinology and Metabolism, Department of Pediatrics, Case Western Reserve University, Rainbow Babies and Children’s Hospital, 11100 Euclid Avenue, 44106–6004, Cleveland, OH, USA

    Douglas S. Kerr MD, PhD

  2. Genetics, Pediatrics, Center for Human Genetics, Case Western Reserve University, Cleveland, OH, USA

    Suzanne D. DeBrosse MD

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  1. Suzanne D. DeBrosse MD
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  2. Douglas S. Kerr MD, PhD
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Correspondence to Douglas S. Kerr MD, PhD .

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  1. , Dept. of Molecular and Human Genetics, Baylor College of Medicine, Baylor Plaza ONE, Houston, 77030, Texas, USA

    Lee-Jun C. Wong

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DeBrosse, S., Kerr, D. (2013). Pyruvate Dehydrogenase Complex Deficiencies. In: Wong, LJ. (eds) Mitochondrial Disorders Caused by Nuclear Genes. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3722-2_19

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