Infantile GM1 Gangliosidosis: Complete Morphology and Histochemistry of Two Autopsy Cases, with Particular Reference to Delayed Central Nervous System Myelination

ABSTRACT: Inborn metabolic errors causing lysosomal storage, such as β-galactosidase deficiency (G_M1 gangliosidosis [G_M1]), have well-recognized effects on cellular function and morphology. In some classically “neuronal” storage diseases, including G_M1, neuroradiologic observations of infants have suggested a delay in myelination on the basis of persistently “immature” signal intensities monitored over time. We sought to evaluate in a semiquantitative fashion the pattern and degree of myelination in two infantile G_M1 patients, one boy and one girl, autopsied at 15 months of age. We assigned myelination degrees for defined sites on an ordinal scale of 0 to 4, and compared them to published population-based values for autopsied infants. In both patients, earlier-myelinating structures were comparable in development to that expected for postconceptional age, whereas later-myelinating structures were delayed. These data correlate well with the neuroradiologic diagnosis of myelination delay in these infants and suggest that the metabolic defect has a primary influence on myelin development, in addition to effects related to neuronal storage. Furthermore, our analysis by light and electron microscopy and lectin histochemistry of both CNS and systemic tissues, several of which had not been described, add to the understanding of the stored material in different cell types.