Loss of Small Peripheral Sensory Neurons in Fabry Disease: Histologic and Morphometric Evaluation of Cutaneous Nerves, Spinal Ganglia, and Posterior Columns

Quantitative histologic studies of peripheral sensory neurons at the peripheral nerve (sural nerve) and spinal ganglion (L-3) levels showed preferential loss of small myelinated and unmyelinated fibers and of small cytons (cell bodies) of spinal ganglia in a patient with long-term Fabry disease. Myelinated fiber density in the fasciculus gracilis of the spinal cord (C-1 and C-8) initially was less than in a control specimen. However, further analysis in three additional controls indicated that fiber density fell within the normal range. In a second typical case, sural nerve biopsy showed a selective decrease of small myelinated and unmyelinated fibers. Painfulness and loss of sweating characteristic of this disorder may result from degeneration of small fibers. There were axonal degeneration and segmental demyelination, probably due to a metabolic derangement in cytons. At the cyton, degenerating neurons were recognized by histologic abnormalities, decreased endoplasmic reticulum, and deposition of lipid granules.