encephalomyopathic mtDNA depletion syndrome with methylmalonic aciduria

Pathology

 germline mutations in encephalomyopathic mtDNA depletion syndrome with methylmalonic aciduria (MIM.612073)

• markedly decreased succinyl-CoA synthetase activity due to a deleterious mutation in SUCLA2, the gene encoding the beta subunit of the ADP-forming succinyl-CoA synthetase ligase,
• Succinyl-CoA synthetase is invariably in a complex with mitochondrial nucleotide diphosphate kinase.

SUCLA2 is the gene encoding the beta subunit of the ADP-forming succinyl-CoA synthetase ligase.

See also

 mitochondrial DNA depletion syndrome (MDDS)

• The mitochondrial DNA depletion syndrome (mtDNA depletion syndrome or MDDS) is a quantitative defect of mtDNA resulting from dysfunction of one of several nuclear-encoded factors responsible for maintenance of mitochondrial deoxyribonucleoside triphosphate (dNTP) pools or replication.

References

 Carrozzo, R.; Dionisi-Vici, C.; Steuerwald, U.; Lucioli, S.; Deodato, F.; Di Giandomenico, S.; Bertini, E.; Franke, B.; Kluijtmans, L. A. J.; Meschini, M. C.; Rizzo, C.; Piemonte, F.; Rodenburg, R.; Santer, R.; Santorelli, F. M.; van Rooij, A.; Vermunt-de Koning, D.; Morava, E.; Wevers, R. A. : SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia, and deafness. Brain 130: 862-874, 2007. PubMed ID : 17301081

 Elpeleg, O.; Miller, C.; Hershkovitz, E.; Bitner-Glindzicz, M.; Bondi-Rubinstein, G.; Rahman, S.; Pagnamenta, A.; Eshhar, S.; Saada, A. : Deficiency of the ADP-forming succinyl-CoA synthase activity is associated with encephalomyopathy and mitochondrial DNA depletion. Am. J. Hum. Genet. 76: 1081-1086, 2005. PubMed ID : 15877282

 Johnson, J. D.; Mehus, J. G.; Tews, K.; Milavetz, B. I.; Lambeth, D. O. : Genetic evidence for the expression of ATP- and GTP-specific succinyl-CoA synthetases in multicellular eucaryotes. J. Biol. Chem. 273: 27580-27586, 1998. PubMed ID : 9765291

 Ostergaard, E.; Hansen, F. J.; Sorensen, N.; Duno, M.; Vissing, J.; Larsen, P. L.; Faeroe, O.; Thorgrimsson, S.; Wibrand, F.; Christensen, E.; Schwartz, M. : Mitochondrial encephalomyopathy with elevated methylmalonic acid is caused by SUCLA2 mutations. Brain 130: 853-861, 2007. PubMed ID : 17287286