A Novel SUCLA2 Mutation in a Portuguese Child Associated With "Mild" Methylmalonic Aciduria. (February 2015)

• Record Type: Journal Article
• Authors: Nogueira, Célia; Meschini, Maria Chiara; Nesti, Claudia; Garcia, Paula; Diogo, Luisa; Valongo, Carla; Costa, Ricardo; Videira, Arnaldo; Vilarinho, Laura; Santorelli, Filippo M.
• Is Part Of: Journal of child neurology. Volume 30:Number 2(2015:Feb.)
• Page Start: 228
• Page End: 232
• Publication Date: 2015-02
• Subjects: SUCLA2 -- methylmalonic aciduria -- mitochondrial DNA depletion -- encephalomyopathy -- succinate-coenzyme A ligase; Nervous system -- Diseases -- Periodicals; 618.928
• DOI: 10.1177/0883073814527158
• Languages: English
• ISSNs: 0883-0738

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.