The system for oxidative phosphorylation (OXHOS) is comprised of five multiprotein complexes, which produces ATP as an energy source for the cell. Hence, complex II deficiency results in a reduced ATP production and manifests as a very heterogenous mitochondrial disorder.
SDHA as part of complex II is involved in two coupled metabolic pathways - it oxidises succinate to fumarate in the tricarboxylic acid cycle and the electrons are used to reduce FAD to FADH2, ultimately reducing ubiquinone to ubiquinol in the system for OXPHOS.
Pathogenic variants in SDHAinclude missense-, splice-site-, nonsense- and frameshift-variants. Also copy number variations are described. Diagnostic testing may involve measuring enzymatic activity of complex II and molecular genetic testing by sequencing SDHAand others SDHx and assembly factors using a gene panel.
SDHA