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

作者：Nogueira Celia; Meschini Maria Chiara; Nesti Claudia; Garcia Paula; Diogo Luisa; Valongo Carla; Costa Ricardo; Videira Arnaldo; Vilarinho Laura; Santorelli Filippo M^*

来源：Journal of Child Neurology, 2015, 30(2): 228-232.

DOI：10.1177/0883073814527158

• SUCLA2
• methylmalonic aciduria
• mitochondrial DNA depletion
• encephalomyopathy
• succinate-coenzyme A ligase

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 and 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.

• 出版日期2015-2