Objectives: To present a case in which leukodystrophy was a distinct and prominent imaging finding. Case Report: The index case presented at 22 months of age for investigation of developmental delay, anemia, hypothyroidism and slightly dysmorphic features. MRI disclosed supratentorial leukoencephalopathy, sparing intense capsule, basal ganglia and thalami. Brainstem was also affected with signal intensity in T2 -weighted images. In the differential diagnosis mitochondrial and "vanishing white matter" disease were considered. On subsequent follow-up the patient manifested an episode of acute encephalopathy with hypoketotic hypoglycemia, metabolic acidosis and hyperammonemia. Urinary organic acids and acylcarnitine profile were strongly abnormal and suggestive of GAII. Conclusion/Discussion: The unusual phenotype of this patient, characterized by progressive encephalopathy, along with the MRI findings were misleading and suggesting a leukodystrophic process rather than an organic aciduria. The presence of leukodystrophy should always prompt the investigation for an organic aciduria, even in the absence of acute decompensation. Background: The role of glial cells in glutaric acidemia I (GA-I) pathogenesis is mostly unknown. Objectives: We evaluated the effects of pathophysiological concentrations of glutaric acid (GA) and lysine on glial cells from the glutaryl-CoA dehydrogenase (GCDH) knockout (KO) mouse model. Methods: Functional and morphological parameters were analyzed in cortical and striatal cultures of astrocytes and oligodendrocytes from newborn C57 GCDH KO and wild type mice submitted to 5 and 10 mM GA or 10 mM lysine during 24 hours. Results: Lysine caused mitochondrial dysfunction, as verified by decreased mitochondrial potential in KO cultured astrocytes, measured by ratiometric fluorescence of the JC1 probe and MTT activity. Cellular glutathione levels decreased 25%, whereas carboxy-H2DFFDA signals augmented 35%. Astrocytic proliferation was increased by 30% related to untreated cells. GA causes similar effects without significant differences among the concentrations employed. No changes in glutamate transporter GLT1 and glutamine synthase expressions were found in KO astrocytes even upon GA or lysine exposure. In addition, 80% less of oligodendrocyte progenitors were obtained from the KO cultures.