Infantile neuroaxonal dystrophy associated with α-N-acetylgalactosaminidase deficiency: on relating axonal spheroids to a lysosomal enzyme deficiency
Appropriately for a symposium on peripheral neuropathy, this contribution considers the pathogenesis of distal axonal spheroids in two brothers with biopsy-proven infantile neuroaxonal dystrophy (INAD), who also have a well-delineated inherited defect in lysosomal glycoprotein degradation: α-N-acetylgalactosaminidase deficiency. The possibility that the membranous content of their distal axonal spheroids directly represents the storage product of their lysosomal enzymatic defect is considered. The occurrence of ultra-structurally identical membranous spheroids in inherited and acquired human and experimental diseases unrelated to this lysosomal defect, current knowledge of neuronal lysosomes and of the synthesis, axonal transport, and degradation of glycoproteins in neurons, and the absence of this lysosomal enzymatic defect in cells from unrelated autopsy-proven cases of INAD, all suggest that the axonal spheroids in these brothers either are related to their lysosomal deficiency by highly indirect and undemonstrated paths, or that their membranous axonal spheroids are unrelated causally to their lysosomal deficiency and that ultrastructural storage in this new lysosomal disease remains to be demonstrated by more sensitive and specific methods.
KeywordsFabry Disease Sural Nerve Biopsy Retrograde Axonal Transport Diabetic Autonomic Neuropathy Axonal Spheroid
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