Patients may present with vomiting, dehydration, lethargy, and encephalopathy. Some evidence suggests that propionic acidemia predisposes patients to bilateral basal ganglia infarcts involving the caudate, putamen, and globus pallidus. A defect in this metabolic pathway produces several potentially toxic metabolites. Hamilton et al suggested that metabolites of the dysfunctional propionic acid and methylmalonic acid pathways may be selectively toxic to the endothelial cells in the basal ganglia.
Endothelial damage is the presumed basis for strokes.
The authors confirmed that basal ganglia lesions were not due to hypoxemia, because the hippocampus, which is relatively more sensitive to hypoxemia, was spared. An alternative hypothesis implicates direct basal ganglia damage due to cytochrome-c oxidase dysfunction. Accumulation of propionic acid apparently results in an abnormal cytochrome-c oxidase. This excess glutamate may be excitotoxic to neuronal cells in the basal ganglia. True incidence may be higher, since many neonatal deaths may be caused by undocumented acidopathies.