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Giant axonal neuropathy (GAN) is a disease characterized by a slowly progressive neuropathy and signs of central involvement, manifested by visual impairment, corticospinal tract dysfunction, ataxia, and dementia. Pathological hallmarks of the disease include axonal swellings packed with neurofilaments in both peripheral and central nervous systems, and accumulations of intermediate filaments in Schwann cells, fibroblasts, melanocytes, endothelial, and Langerhans cells. Rosenthal fibers, sometimes appearing in masses and mimicking Alexander's disease, emerge as a conspicuous characteristic in longstanding GAN.

Sural nerve biopsy was performed on a six-year-old girl with a slowly progressive distal mixed polyneuropathy. The nerve fiber population was reduced, and of those remaining, approximately half were greatly enlarged, measuring up to 35 microns in cross section. Longitudinal sections showed axonal enlargement to be segmental. Ultrastructurally, swollen axonal segments were filled with neurofilaments in closely-packed swirls which appeared to tie on occasion into granular electron-opaque condensations. Both, myelinated and unmyelinated fibers were involved, and some degree of onion-bulb formation was observed. Although masses of neurofilaments are found in peripheral axons in other disorders, none approaches the proportions encountered in this unique case.