In our cohort, diagnostic metabolic investigations were unremarkable, including CSF neurotransmitters, except for the reduction of CSF 5-methyltetrahydrofolate levels in patients 1 and 2. In both patients, calcium folinate administration was started but did not lead to discernible clinical improvement. Brain MRI (figure 2) was unremarkable in patients 4 and 7, while inconsistent changes were detected in the remaining patients (microcephaly, macrocephaly, progressive cerebral atrophy with dilated ventricles and subarachnoid spaces, caudate volume loss, and dysmorphic corpus callosum). In 1 patient (patient 5), a focal lesion involving the gray and white matter of the left frontal lobe was identified and confirmed as a diffuse astrocytoma (WHO grade 2) after surgical removal.
