title: A novel SUCLA2 mutation in a Portuguese child associated with "mild" methylmalonic aciduria.
abstract: Succinyl-coenzyme A synthase is a mitochondrial matrix enzyme that catalyzes the reversible synthesis of succinate and adenosine triphosphate (ATP) from succinyl-coenzyme A and adenosine diphosphate (ADP) in the tricarboxylic acid cycle. This enzyme is made up of α and β subunits encoded by SUCLG1 and SUCLA2, respectively. We present a child with severe muscular hypotonia, dystonia, failure to thrive, sensorineural deafness, and dysmorphism. Metabolic investigations disclosed hyperlactacidemia, moderate urinary excretion of methylmalonic acid, and elevated levels of C4-dicarboxylic carnitine in blood. We identified a novel homozygous p.M329V in SUCLA2. In cultured cells, the p.M329V resulted in a reduced amount of the SUCLA2 protein, impaired production of mitochondrial ATP, and enhanced production of reactive oxygen species, which was partially reduced by using 5-aminoimidazole-4-carboxamide ribonucleotide in the culture medium. Expanding the array of SUCLA2 mutations, we suggested that reactive oxygen species scavengers are likely to impact on disease prognosis.
authors.affiliation: Department of Genetics, National Institute of Health, INSA, Porto, Portugal.
authors.forename: Célia
authors.initials: C
authors.lastname: Nogueira
authors.affiliation: IRCCS Stella Maris, Pisa, Italy.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Meschini
authors.affiliation: IRCCS Stella Maris, Pisa, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Nesti
authors.affiliation: Hereditary Metabolic Diseases Unit, Hospital Pediátrico, CHUC, Coimbra, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Garcia
authors.affiliation: Hereditary Metabolic Diseases Unit, Hospital Pediátrico, CHUC, Coimbra, Portugal.
authors.forename: Luisa
authors.initials: L
authors.lastname: Diogo
authors.affiliation: Department of Genetics, National Institute of Health, INSA, Porto, Portugal.
authors.forename: Carla
authors.initials: C
authors.lastname: Valongo
authors.affiliation: Pediatric Department, Cova da Beira Hospital Center, Covilhã, Portugal.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Costa
authors.affiliation: ICBAS- Instituto de Ciências Biomédicas de Abel Salazar, University of Porto, Porto, Portugal.
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Videira
authors.affiliation: Department of Genetics, National Institute of Health, INSA, Porto, Portugal.
authors.forename: Laura
authors.initials: L
authors.lastname: Vilarinho
authors.affiliation: IRCCS Stella Maris, Pisa, Italy filippo3364@gmail.com.
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Santorelli
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis / Q000235:genetics*; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D013389:Succinate-CoA Ligases / Q000235:genetics*
chemical_list: D013389:Succinate-CoA Ligases; C518788:SUCLA2 protein, human
keywords: SUCLA2; encephalomyopathy; methylmalonic aciduria; mitochondrial DNA depletion; succinate-coenzyme A ligase