Deficiency of the alpha subunit of succinate-coenzyme A ligase causes fatal infantile lactic acidosis with mitochondrial DNA depletion.
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.
Ostergaard
Elsebet
E
Department of Clinical Genetics, National University Hospital Rigshospitalet, Copenhagen, Denmark. elsebet.oestergaard@rh.regionh.dk
Christensen
Ernst
E
Kristensen
Elisabeth
E
Mogensen
Bodil
B
Duno
Morten
M
Shoubridge
Eric A
EA
Wibrand
Flemming
F
D000140:Acidosis, Lactic / Q000235:genetics*; D004272:DNA, Mitochondrial; D017809:Fatal Outcome; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D028361:Mitochondrial Diseases / Q000235:genetics; D010375:Pedigree; D021122:Protein Subunits; D013389:Succinate-CoA Ligases / Q000235:genetics*
D004272:DNA, Mitochondrial; D021122:Protein Subunits; D013389:Succinate-CoA Ligases