Multiple oxidative phosphorylation deficiencies in severe childhood multi-system disorders due to polymerase gamma (POLG1) mutations

Maaike C. De Vries, Richard J. Rodenburg, Eva Morava, Edwin P.M. Van Kaauwen, Henk Ter Laak, Reinier A. Mullaart, Irina N. Snoeck, Peter M. Van Hasselt, Peter Harding, Lambert P.W. Van Den Heuvel, Jan A.M. Smeitink

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Failure to thrive, feeding difficulties, variable forms of infantile epilepsy or psychomotor developmental delay and hypotonia were the most frequent clinical disease presentations in eight children with combined oxidative phosphorylation enzyme complex deficiencies carrying mutations in the polymerase gamma (POLG1) gene. Five out of eight patients developed severe liver dysfunction during the course of the disease. Three of these patients fulfilled the disease criteria for Alpers syndrome. Most children showed deficiencies of respiratory chain enzyme complexes I and III, in combination with complex II, complex IV and/or PDHc in muscle, whereas in fibroblasts normal enzyme activities were measured. All children carried homozygous or compound heterozygous mutations in the POLG1 gene, including two novel mutations in association with mtDNA depletion. Conclusion We suggest performing POLG1 mutation analysis in children with combined oxidative phosphorylation deficiencies in muscle, even if the clinical picture is not Alpers syndrome.

Original languageEnglish (US)
Pages (from-to)229-234
Number of pages6
JournalEuropean Journal of Pediatrics
Volume166
Issue number3
DOIs
StatePublished - Mar 1 2007

Keywords

  • Combined OXPHOS deficiencies
  • Mitochondrial medicine
  • POLG1

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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