A Novel SUCLA2 Mutation in a Portuguese Child Associated With "Mild" Methylmalonic Aciduria

• Autor(a) principal: Nogueira, Célia
• Data de Publicação: 2014
• Outros Autores: Meschini, M.C., Nesti, C., Garcia, P., Diogo, L., Valongo, C., Costa, R., Videira, A., Vilarinho, L., Santorelli, F.M.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.18/2818
• topic: SUCLA2; Encephalomyopathy; Methylmalonic Aciduria; Mitochondrial DNA Depletion; Succinate-coenzyme A Ligase; Doenças Genéticas

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.