Pyruvate dehydrogenase E3 binding protein (protein X) deficiency
Article first published online: 13 FEB 2007
Developmental Medicine & Child Neurology
Volume 48, Issue 9, pages 756–760, September 2006
How to Cite
Brown, R. M., Head, R. A., M, A. A., J, J. A., Walter, J. H., Whitehouse, W. P. and Brown, G. K. (2006), Pyruvate dehydrogenase E3 binding protein (protein X) deficiency. Developmental Medicine & Child Neurology, 48: 756–760. doi: 10.1111/j.1469-8749.2006.tb01362.x
- Issue published online: 13 FEB 2007
- Article first published online: 13 FEB 2007
- Accepted for publication 20th February 2006.
Pyruvate dehydrogenase (PDH) deficiency is a major cause of neurological dysfunction and lactic acidosis in infancy and early childhood. The great majority of cases (>80%) result from mutations in the X-linked gene for the E1α subunit of the complex (PDHA1). Mutations in the genes for the other subunits have all been described, but only dihydrolipoamide dehydrogenase (E3) and E3 binding protein (E3BP) defects contribute significantly to the total number of patients with PDH deficiency. Although previously considered rare, with only 13 reported cases, we have found that mutations in PDX1, the gene for the E3 binding protein, are in fact relatively common. Clinical, biochemical, and genetic features of six new patients (four males, two females; age range 15mo-6y) with mutations in this gene are compared with previously reported cases. All patients with E3BP deficiency identified to date have mutations which completely prevent synthesis of the protein product. However, they are generally less severely affected than patients with PDHA1 mutations, although there is considerable overlap in clinical and neuroradiological features.