European Journal of Pediatrics

, Volume 166, Issue 3, pp 229–234

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
Original Paper

DOI: 10.1007/s00431-006-0234-9

Cite this article as:
de Vries, M.C., Rodenburg, R.J., Morava, E. et al. Eur J Pediatr (2007) 166: 229. doi:10.1007/s00431-006-0234-9

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.

Keywords

POLG1Combined OXPHOS deficienciesMitochondrial medicine

Abbreviations

ATP

adenosine triphosphate

CSF

cerebrospinal fluid

ECG

electrocardiography

EEG

electroencephalography

MRI

magnetic resonance imaging

mtDNA

mitochondrial DNA

OXPHOS

oxidative phosphorylation system

PCR

polymerase chain reaction

PDHc

pyruvate dehydrogenase complex

PEO

progressive external ophthalmoplegia

POLG

polymerase gamma

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Maaike C. de Vries
    • 1
    • 6
  • Richard J. Rodenburg
    • 1
  • Eva Morava
    • 1
  • Edwin P. M. van Kaauwen
    • 1
  • Henk ter Laak
    • 1
  • Reinier A. Mullaart
    • 2
  • Irina N. Snoeck
    • 3
  • Peter M. van Hasselt
    • 4
  • Peter Harding
    • 5
  • Lambert P. W. van den Heuvel
    • 1
  • Jan A. M. Smeitink
    • 1
  1. 1.Nijmegen Centre for Mitochondrial Disorders, Departments of Pediatrics, Laboratory of Pediatrics and Neurology and Department of PathologyRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  2. 2.Department of Child NeurologyRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  3. 3.Department of NeurologyJuliana Children’s HospitalDen HaagThe Netherlands
  4. 4.Department of PediatricsAcademic Medical Centre UtrechtUtrechtThe Netherlands
  5. 5.Department of PediatricsKlinikum OldenburgOldenburgGermany
  6. 6.Department of PediatricsRadboud University Nijmegen Medical CentreNijmegenThe Netherlands