Ultrastructural pathology of dermal axons and Schwann cells in lysosomal diseases

Skin tissue specimens, obtained from 60 patients afflicted with a diverse range of lysosomal disorders revealed two groups of lesions within dermal axons, largely unmyelinated ones, particularly within axonal terminals: (1) non-specific mitochondria and dense bodies often enlarging the axonal terminal; and (2) disease-specific lysosomal residual bodies, the latter less frequent depending on the incidence and type of lysosomal disorders, i.e., largely only seen in GM2-gangliosidosis due to hexosaminidase A deficiency and mucolipidosis IV, while the spectrum of lysosomal residual bodies in Schwann cells appeared more variegated, especially due to the occurrence of vacuolar lysosomal residual bodies which were never seen within axons. The most frequent location of abnormal intraaxonal constituents in terminal axons indicates a functionally and morphologically impaired retrograde axonal transport but provides no further evidence as to whether the respective parent nerve cell body has also accumulated lysosomal residual bodies. When studying biopsied skin specimens for diagnosis, axonal terminals beneath the epidermis, about sweat glands, and among smooth muscle cells, ought to be incorporated into a comprehensive electron microscopic examination.