| Main clinical features
|
early-onset metabolic epileptic encephalopathy: soon after birth, hypotonia, feeding difficulties, and global developmental delay even before the onset of seizures in the first year of life; severity is variable, but all patients have severely impaired intellectual development with absent speech and spastic tetraplegia
brain imaging shows cerebral atrophy, thin corpus callosum, cerebellar hypoplasia, and white matter abnormalities
laboratory studies show increased serum lactate and ammonia
GOT2 deficiency impacts the malate-aspartate shuttle and subsequently the overall cellular NADH/NAD+ ratio with consequences for NAD-dependent enzymes and pathways |