Deficiency of the alpha subunit of succinate-coenzyme A ligase causes fatal infantile lactic acidosis with mitochondrial DNA depletion

Am J Hum Genet. 2007 Aug;81(2):383-7. doi: 10.1086/519222. Epub 2007 Jun 4.


Fatal infantile lactic acidosis is a severe metabolic disorder characterized by the onset of lactic acidosis within the 1st d of life and early death. We found a combined respiratory-chain enzyme deficiency associated with mitochondrial DNA (mtDNA) depletion in a small consanguineous family with this disorder. To identify the disease-causing gene, we performed single-nucleotide polymorphism homozygosity mapping and found homozygous regions on four chromosomes. DNA sequencing revealed a homozygous 2-bp deletion in SUCLG1, a gene that encodes the alpha subunit of the Krebs-cycle enzyme succinate-coenzyme A ligase (SUCL). The mtDNA depletion is likely explained by decreased mitochondrial nucleoside diphosphate kinase (NDPK) activity resulting from the inability of NDPK to form a complex with SUCL.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis, Lactic / genetics*
  • DNA, Mitochondrial*
  • Fatal Outcome
  • Female
  • Gene Dosage
  • Humans
  • Infant, Newborn
  • Male
  • Mitochondrial Diseases / genetics
  • Pedigree
  • Protein Subunits*
  • Succinate-CoA Ligases / genetics*


  • DNA, Mitochondrial
  • Protein Subunits
  • Succinate-CoA Ligases

Associated data

  • RefSeq/NM_003849