Magnetic Resonance Spectroscopy in Congenital Metabolic Disorders

Introduction Congenital metabolic disorders refer to inherited defects producing metabolic abnormalities in the human body. Disorders that disrupt the central nervous system (CNS) are of great importance. These disorders produce a paradoxical situation for neuroradiologists and imaging scientists investigating them. One would hypothesize that an error in metabolism would produce either an excess or deficit of a given metabolite. Magnetic resonance spectroscopy (MRS) should be ideally suited for recognizing such errors of metabolism. In a few conditions, proton MRS offers a narrow diagnostic differential. However, for the majority of congenital metabolic disorders, non-distinct imaging and proton spectroscopic presentations, such as volume loss, abnormal T2 signal and reduced N-acetyl aspartate (NAA), are found in the brains of children and adults. The ability to observe metabolic alterations and to recognize them as distinct disorders remains difficult. In principal, two factors limit the application: 1) diminished sensitivity in metabolite detection due to inherently low proton signal and/or concentrations, and 2) poor specificity with common features for distinct metabolic disorders. For pediatrics, additional disadvantages include developmental maturation coupled with progression of disease with multiple primary and secondary features. Regardless a primary or secondary metabolic defect, metabolic disorders should impact cellular function, disrupt at least one of the commonly observed metabolites NAA, creatine and phosphocreatine (Cr & PCr), cholines (Cho)) or demonstrate a pathological metabolite, such as lactate or alanine. The practical usefulness of MRS exists in offering information on staging pathologic processes such as ischemia, altered myelination, gliosis, and neurodegeneration. This presentation will review the spectroscopic features associated with mitochondrial disorders, peroxisomal disorders, amino acid disorders, lysosomal disorders, primary white matter disorders and a few novel disorders. Spectroscopic appearances can differ due to technical factors and change with the age of onset and stage in disease progression. Recent texts [1,2] offer reviews of select metabolic entities from an imaging perspective. In select conditions, MRS will provide the only diagnostic feature found with any imaging examination (i.e. creatine deficiency syndromes). In many situations, MRS will provide only confirmatory diagnostic information to the imaging examination. However, recent studies using MRS indicate potentially a more beneficial role in therapeutic monitoring.