Background: Pelizaeus-Merzbacher disease (PMD) is a rare X-linked recessive neurologic disorder caused by a mutation in the proteolipid protein (PLP) gene on chromosome Xq22. The associated depletion of PLP and severe reduction of other major myelin proteins results in dysmyelination. MRI reveals loss of T1 contrast between gray and affected white matter and T2 hyperintensities of white matter due to elevated water content. Methods: In vivo proton magnetic resonance spectroscopy (MRS) was used to determine cerebral metabolite patterns in five patients with genetically proven PMD. Absolute metabolite concentrations were obtained in cortical gray matter, affected white matter, and basal ganglia and compared to age-matched control values. Results: In comparison to age-matched controls, MRS of affected white matter resembled the metabolite pattern of cortical gray matter, as indicated by increased concentrations of N-acetylaspartate and N-acetylaspartylglutamate (tNAA), glutamine (Gln), myo-inositol (Ins), and creatine and phosphocreatine. Most remarkably, the concentration of choline-containing compounds was reduced. Parietal gray matter and basal ganglia appeared normal but showed a tendency for elevated tNAA, Gln, and Ins. Conclusions: Magnetic resonance spectroscopy (MRS)detected alterations are consistent with enhanced neuroaxonal density, astrogliosis, and reduction of oligodendroglia. These disturbances in cellular composition are in close agreement with the histopathologic features characteristic of dys-and hypomyelination. The proton MRS profile of Pelizaeus-Merzbacher disease (PMD) differs from the pattern commonly observed in demyelinating disorders and allows PMD to be distinguished from other leukodystrophies. Background: Pelizaeus-Merzbacher disease (PMD) is a rare X-linked recessive neurologic disorder caused by a mutation in the proteolipid protein (PLP) gene on chromosome Xq22. The associated depletion of PLP and severe reduction of other major myelin proteins results in dysmyelination . MRI reveals loss of T1 contrast between gray and affected white matter and T2 hyperintensities of white matter due to elevated water content. Methods: In vivo proton magnetic resonance spectroscopy (MRS) was used to determine cerebral metabolite patterns in five patients with genetically proven PMD . Absolute metabolite concentrations were obtained in cortical gray matter, affected white matter, and basal ganglia and compared to age-matched control values. Results: In comparison age-matched controls, MRS of affected white matter resembled the metabolite pattern of cortical gray matter , as indicated by increased concentrations of N-acetylaspartate and N-acetylaspartylglutamate (tNAA), glutamine (Gln), my Parietal gray matter and basal ganglia have normal but showed a tendency for elevated tNAA, Gln, and Ins. Conclusions: Magnetic resonance spectroscopy (MRS) detected alterations are consistent with enhanced neuroaxonal density, astrogliosis, and reduction of oligodendroglia. These disturbances in cellular composition are in close agreement with the histopathological features of dys-and hypomyelination. The proton MRS profile of Pelizaeus-Merzbacher disease PMD) differs from the pattern commonly observed in demyelinating disorders and allows PMD to be distinguished from other leukodystrophies.