Neonatal lactic acidosis with methylmalonic aciduria due to novel mutations in the SUCLG1 gene

Pediatr Int. 2011 Dec;53(6):921-5. doi: 10.1111/j.1442-200X.2011.03412.x.

Abstract

Background: Succinyl-coenzyme A ligase (SUCL) is a mitochondrial enzyme that catalyses the reversible conversion of succinyl-coenzyme A to succinate. SUCL consists of an α subunit, encoded by SUCLG1, and a β subunit, encoded by either SUCLA2 or SUCLG2. Recently, mutations in SUCLG1 or SUCLA2 have been identified in patients with infantile lactic acidosis showing elevated urinary excretion of methylmalonate, mitochondrial respiratory chain (MRC) deficiency, and mitochondrial DNA depletion.

Methods: Case description of a Japanese female patient who manifested a neonatal-onset lactic acidosis with urinary excretion of methylmalonic acid. Enzymatic analyses (MRC enzyme assay and Western blotting) and direct sequencing analysis of SUCLA2 and SUCLG1 were performed.

Results: MRC enzyme assay and Western blotting showed that MRC complex I was deficient. SUCLG1 mutation analysis showed that the patient was a compound heterozygote for disease-causing mutations (p.M14T and p.S200F).

Conclusion: For patients showing neonatal lactic acidosis and prolonged mild methylmalonic aciduria, MRC activities and mutations of SUCLG1 or SUCLA2 should be screened for.

Publication types

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

MeSH terms

  • Acidosis, Lactic / complications
  • Acidosis, Lactic / genetics*
  • Acidosis, Lactic / metabolism
  • Acyl Coenzyme A / genetics*
  • Amino Acid Metabolism, Inborn Errors / complications
  • Amino Acid Metabolism, Inborn Errors / genetics*
  • Amino Acid Metabolism, Inborn Errors / metabolism
  • Blotting, Western
  • DNA / genetics*
  • DNA Mutational Analysis
  • Fatal Outcome
  • Female
  • Humans
  • Infant, Newborn
  • Mutation*

Substances

  • Acyl Coenzyme A
  • DNA
  • succinyl-coenzyme A

Supplementary concepts

  • Methylmalonic acidemia