Developmental Medicine & Child Neurology



Original Articles

Pyruvate dehydrogenase E3 binding protein (protein X) deficiency


RM Brown  a1, RA Head  a1, AAM Morris  a2, JAJ Raiman  a3, JH Walter  a2, WP Whitehouse  a4 and GK Brown  a1 c1
a1 Genetics Unit, Department of Biochemistry, University of Oxford, Oxford, UK.
a2 Willink Biochemical Genetics Unit, Royal Manchester Children's Hospital, Manchester, UK.
a3 Guy's and St Thomas' Hospital, London, UK.
a4 School of Human Development, University of Nottingham, Nottingham, UK.

Abstract

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.

(Published Online August 14 2006)
(Accepted February 20 2006)


Correspondence:
c1 Genetics Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK. E-mail: garry.brown@bioch.ox.ac.uk