Cerebral metabolic abnormalities in five children with infantile (1), late infantile (1), and juvenile (3) neuronal ceroid lipofuscinosis (NCL) were noninvasively assessed by localized proton magnetic resonance spectroscopy (MRS). Infantile NCL was characterized by a complete loss of N-acetylasparate (NAA, neuronal marker), a marked reduction of cretinise (Cr) and choline-containing compounds (Cho), and an elevation of myo-inositol (Ins, glial marker) and lactate (Lac) in both grey and white matter. In contrast to the infantile forms, juvenile NCL exhibited normal metabolic profiles. In one patient disease progression was indicated by reduced NAA and Cr in grey matter in a follow-up study after four years. The present findings in NCL are consistent with irreversible and generalized neuroaxonal loss as well as alterations of white matter glia similar disturbances correlates with clinical symptoms and decreasing age of onset.