TY - JOUR
T1 - Multiple oxidative phosphorylation deficiencies in severe childhood multi-system disorders due to polymerase gamma (POLG1) mutations
AU - De Vries, Maaike C.
AU - Rodenburg, Richard J.
AU - Morava, Eva
AU - Van Kaauwen, Edwin P.M.
AU - Ter Laak, Henk
AU - Mullaart, Reinier A.
AU - Snoeck, Irina N.
AU - Van Hasselt, Peter M.
AU - Harding, Peter
AU - Van Den Heuvel, Lambert P.W.
AU - Smeitink, Jan A.M.
N1 - Funding Information:
Acknowledgements Research at the NCMD is funded by the Radboud University Nijmegen Medical Centre, the Prinses Beatrix Fonds, the Dutch Scientific Organization and the European Union (EUMITOCOMBAT and MitoCircle grants).
PY - 2007/3
Y1 - 2007/3
N2 - 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.
AB - 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.
KW - Combined OXPHOS deficiencies
KW - Mitochondrial medicine
KW - POLG1
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U2 - 10.1007/s00431-006-0234-9
DO - 10.1007/s00431-006-0234-9
M3 - Article
C2 - 16957900
AN - SCOPUS:33847612847
SN - 0943-9676
VL - 166
SP - 229
EP - 234
JO - European Journal of Pediatrics
JF - European Journal of Pediatrics
IS - 3
ER -