European Journal of Pediatrics

, Volume 169, Issue 2, pp 201–205 | Cite as

A novel missense mutation in SUCLG1 associated with mitochondrial DNA depletion, encephalomyopathic form, with methylmalonic aciduria

  • Elsebet OstergaardEmail author
  • Marianne Schwartz
  • Mustafa Batbayli
  • Ernst Christensen
  • Ola Hjalmarson
  • Gittan Kollberg
  • Elisabeth Holme
Original Paper


Mitochondrial DNA depletion, encephalomyopathic form, with methylmalonic aciduria is associated with mutations in SUCLA2, the gene encoding a β subunit of succinate-CoA ligase, where 17 patients have been reported. Mutations in SUCLG1, encoding the α subunit of the enzyme, have been reported in only one family, where a homozygous 2 bp deletion was associated with fatal infantile lactic acidosis. We here report a patient with a novel homozygous missense mutation in SUCLG1, whose phenotype is similar to that of patients with SUCLA2 mutations.


Methylmalonic aciduria SUCLG1 SUCLA2 mtDNA depletion Encephalomyopathy Succinate-CoA ligase 


  1. 1.
    Carrozzo R, Donisi-Vici C, Steuerwald U et al (2007) SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia and deafness. Brain 130:862–874. doi: 10.1093/brain/awl389 CrossRefPubMedGoogle Scholar
  2. 2.
    Cho MH, Ciulla D, Klanderman BJ et al (2008) High-resolution melting curve analysis of genomic and whole-genome amplified DNA. Clin Chem 2008(October):16Google Scholar
  3. 3.
    Elpeleg O, Miller C, Hershkovitz E et al (2005) Deficiency of the ADP-forming succinyl-CoA synthase activity is associated with encephalomyopathy and mitochondrial DNA depletion. Am J Hum Genet 76:1081–1086. doi: 10.1086/430843 CrossRefPubMedGoogle Scholar
  4. 4.
    Johnson JD, Mehus JG, Tews K et al (1998) Genetic evidence for the expression of ATP- and GTP-specific succinyl-CoA synthetases in multicellular eucaryotes. J Biol Chem 273:27580–27586. doi: 10.1074/jbc.273.42.27580 CrossRefPubMedGoogle Scholar
  5. 5.
    Kadrmas EF, Ray PD, Lambeth DO (1991) Apparent ATP-linked succinate thiokinase activity and its relation to nucleoside diphosphate kinase in mitochondrial matrix preparations from rabbit. Biochim Biophys Acta 1074:339–346PubMedGoogle Scholar
  6. 6.
    Kavanaugh-Black A, Connolly DM, Chugani SA, Chakrabarty AM (1994) Characterization of nucleoside-diphosphate kinase from Pseudomonas aeruginosa: complex formation with succinyl-CoA synthetase. Proc Natl Acad Sci U S A 91:5883–5887. doi: 10.1073/pnas.91.13.5883 CrossRefPubMedGoogle Scholar
  7. 7.
    Kowluru A, Tannous M, Chen HQ (2002) Localization and characterization of the mitochondrial isoform of the nucleoside diphosphate kinase in the pancreatic beta cell: evidence for its complexation with mitochondrial succinyl-CoA synthetase. Arch Biochem Biophys 398:160–169. doi: 10.1006/abbi.2001.2710 CrossRefPubMedGoogle Scholar
  8. 8.
    Lambeth DO (2006) Reconsideration of the significance of substrate-level phosphorylation in the citric acid cycle. Biochem Mol Biol Educ 34:21–29. doi: 10.1002/bmb.2006.49403401021 CrossRefGoogle Scholar
  9. 9.
    Lambeth DO, Tews KN, Adkins S et al (2004) Expression of two succinyl-CoA synthetases with different nucleotide specificities in mammalian tissues. J Biol Chem 279:36621–36624. doi: 10.1074/jbc.M406884200 CrossRefPubMedGoogle Scholar
  10. 10.
    Ostergaard E, Christensen E, Kristensen E et al (2007) Deficiency of the alpha subunit of succinate-coenzyme A ligase causes fatal infantile lactic acidosis with mitochondrial DNA depletion. Am J Hum Genet 81:383–387. doi: 10.1086/519222 CrossRefPubMedGoogle Scholar
  11. 11.
    Ostergaard E, Hansen FJ, Sorensen N et al (2007) Mitochondrial encephalomyopathy with elevated methylmalonic acid is caused by SUCLA2 mutations. Brain 130:853–861. doi: 10.1093/brain/awl383 CrossRefPubMedGoogle Scholar
  12. 12.
    Tulinius MH, Holme E, Kristiansson B et al (1991) Mitochondrial encephalomyopathies in childhood. I. Biochemical and morphologic investigations. J Pediatr 119:242–250. doi: 10.1016/S0022-3476(05) 80734-6 CrossRefPubMedGoogle Scholar
  13. 13.
    Zinn AB, Kerr DS, Hoppel CL (1986) Fumarase deficiency: a new cause of mitochondrial encephalomyopathy. N Engl J Med 315:469–475PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Elsebet Ostergaard
    • 1
    Email author
  • Marianne Schwartz
    • 1
  • Mustafa Batbayli
    • 1
  • Ernst Christensen
    • 1
  • Ola Hjalmarson
    • 2
  • Gittan Kollberg
    • 3
  • Elisabeth Holme
    • 3
  1. 1.Department of Clinical Genetics 4062National University Hospital RigshospitaletCopenhagenDenmark
  2. 2.Department of PediatricsGothenburg UniversityGothenburgSweden
  3. 3.Department of Clinical ChemistrySahlgrenska University HospitalGothenburgSweden

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