Morphologic appearance and metabolic disturbances of the brain of a patient with L-2-hydroxyglutaric acidemia were investigated with use of magnetic resonance imaging and localized proton magnetic resonance spectros-copyin vivo. Whereas magnetic resonance imaging revealed increased internal and external ccrebrospinal fluid spaces as well as patchy white matter lesions, metabolic deviations included a 50% decrease of N-acetylaspartate (neuronal marker), a 75% increase ofmyo-inositol (glial marker), and a 40% decrease of choline-containing compounds in white matter relative to age-matched controls. A clinical deterioration of the patient was clearly reflected in a follow-up examination 22 mo later, resulting in a further reduction of N-acetylaspartate and a more pronounced enhancement ofmyo-inositol. No elevation of lactate was observed. The magnetic resonance spectroscopy findings are in line with a generalized neurodegcnerative process in L-2-hydroxyglutaric acidemia but also suggest a defect in phosphatidyl inositol metabolism of glial cells.