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

Elsebet Ostergaard, Ernst Christensen, Elisabeth Kristensen, Bodil Mogensen, Morten Duno, Eric A Shoubridge, Flemming Wibrand

Department of Clinical Genetics, National University Hospital Rigshospitalet, Copenhagen, Denmark. elsebet.oestergaard@rh.regionh.dk

American journal of human genetics 2007 Aug

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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.

Citation

Elsebet Ostergaard, Ernst Christensen, Elisabeth Kristensen, Bodil Mogensen, Morten Duno, Eric A Shoubridge, Flemming Wibrand. Deficiency of the alpha subunit of succinate-coenzyme A ligase causes fatal infantile lactic acidosis with mitochondrial DNA depletion. American journal of human genetics. 2007 Aug;81(2):383-7