Abnormal Lipopigments and Lysosomal Residual Bodies in Metachromatic Leukodystrophy

Abstract

Ultrastructurally, metachromatic leukodystrophy (MLD) is marked by characteristic features such as herringbone, prismatic and tufaceous patterns which are typically encountered within oligodendrocytes of the central nervous system (CNS) and in Schwann cells (PNS). These patterns can be documented in late infantile, juvenile, and adult forms. In the latter, aging of the ailing individual adds another component, the accumulation of lipopigments which are marked by an opaque supposedly lipid droplet and a granular component. While MLD-specific lysosomal residual bodies occur in myelinforming cells, lipopigments accrue in neurons and to a lesser degree in astrocytes. MLD represents a unique example in which these two separate lysosomal storage processes combine to form a wide spectrum of ultrastructurally divergent MLD-lipopigments affecting several cell type in the CNS and PNS. Lipopigments and MLD-specific lysosomal inclusions also assemble in sweat gland epithelial cells again combined within the same residual body and in Schwann cells of non-myelinated axons which may also regularly display lipopigments, contrary to Schwann cells of myelinated axons. Comparative studies on sweat glands in childhood and adult forms confirm the earlier observations that composite MLD-lipopigments are frequent in adult MLD. Thus, although lipopigment formation and MLD are different processes, their common occurrence in MLD provides evidence of the mutual morphogenic influence which results in a diversified population of MLD-lipopigments. Whether there is absolute increase of lipopigment formation beyond the age-related level remains to be clarified by quantitative and morphometric data. The presence of lipopigments in childhood MLD in sweat gland epithelial cells favors the concept of accelerated lipopigment formation while the lysosomal compartment is already stimulated by an inborn error of lysosomal metabolism. Whether this principle also prevails in adult forms of other non-MLD lysosomal disorders remains to be elucidated by respective ultrastructural investigations.