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

• Published in: European journal of pediatrics Vol. 166; no. 3; pp. 229 - 234
• Main Authors: DE VRIES, Maaike C, RODENBURG, Richard J, SMEITINK, Jan A. M, MORAVA, Eva, VAN KAAUWEN, Edwin P. M, TER LAAK, Henk, MULLAART, Reinier A, SNOECK, Irina N, VAN HASSELT, Peter M, HARDING, Peter, VAN DEN HEUVEL, Lambert P. W
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01.03.2007; Berlin Springer Nature B.V
• Subjects: Biological and medical sciences; Children; Diffuse Cerebral Sclerosis of Schilder - genetics; Diffuse Cerebral Sclerosis of Schilder - physiopathology; DNA Mutational Analysis; DNA Polymerase gamma; DNA-Directed DNA Polymerase - genetics; Electron transport; Enzymatic activity; Enzymes; Epilepsy; Fatal Outcome; Female; Fibroblasts; General aspects; Humans; Infant; Liver diseases; Male; Medical sciences; Mitochondrial Diseases - genetics; Mitochondrial Diseases - physiopathology; Mitochondrial DNA; Mutation; Oxidative phosphorylation; Patients; Phosphorylation; Human; Multiple handicap; Pediatrics; Deficiency; System; Medicine; Mitochondria; Oxidative phosphorylation; Combined OXPHOS deficiencies; Mitochondrial medicine; Genetics; Mutation; POLG1; Severe; Child
• ISSN: 0340-6199; 1432-1076
• DOI: 10.1007/s00431-006-0234-9

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.