Type of mutation:
Multiple pathogenic variants have been reported so far including different homozygous missense mutations, a homozygous nonsense mutation and different compound heterozygous mutations.
Suspected pathophysiologic mechanism:
AGC1, or aralar, is one of the two isoforms of the asparate-glutamate carrier important for the malate-aspartate shuttle (MAS) and is mainly expressed in the brain. It shuttles electrons from the cytosol into the mitochondria to reduce NAD+ to NADH, since the mitochondrial membrane is impermeable for NADH. The MAS is important in mitochondrial NADH supply during oxidative phosphorylation when glucose is the substrate. However, the pathophysiologic mechanism of this disorder remains unclear and under investigation.
SLC25A12