Abnormalities of Developing White Matter in Lysosomal Storage Diseases

Inborn metabolic errors causing lysosomal storage have well-recognized effects on neuronal function and morphology. In some classically "neuronal" storage diseases, however, neuroradiologic observations of infants have suggested a delay in central nervous system myelination based on persistently "immature" signal intensities monitored over time. This review summarizes reported neuropathologic evaluations of central white matter in infantile and juvenile patients and in corresponding animal models with lysosomal storage disorders. The observed neuropathology is examined in light of published studies of the biochemistry and microscopic anatomy of normal myelinogenesis. Finally, arguments are advanced that at least part of the deficiency of white matter is attributable to direct effects of the metabolic state on oligodendrocyte maturation and function, in addition to secondary effects on neurons and their axons.