Giant Axonal Neuropathy in 2 Siblings: A Generalized Disorder of Intermediate Filaments

Abstract

The authors report the clinical details and progress over 15 years of 2 siblings with giant axonal neuropathy with multisystem involvement. Changes in intermediate filaments (IF) were found in myelinated and unmyelinated fiber axons of the peripheral nerve and in Schwann cells, endothelial cells of skin vessels, skin fibro-cytes and melanocytes, confirming a generalized disorder of IF organization.

Giant Axonal Degeneration: Scanning Electron Microscopic and Biochemical Study of Scalp Hair

“…Kretschmar et al [6] demonstrated longitudinal groov ing in hair of a GAD patient by means of SEM. confirmed by Guazzi et al [4] using the same technique. Buissonnière et al…”

“…Although 28 cases of GAD have been reported since 1972, examination of the scalp hair has been done in only a few instances, despite its pathognomonic appearance [3][4][5][6][7],…”

Giant axonal disease: Report of eight cases

“…Lesions in the brain, cerebellum and spinal cord can cause mental retardation, dysmetria, seizures, nystagmus, and dysarthria, as well as signs of spasticity. Scoliosis, kyphosis, optic atrophy, ophthalmoplegia, and epilepsy are reported less commonly [1,6,7]. Involvement of the cerebral cortex, cerebellum, brainstem, anterior horn cells, and pyramidal tracts was also shown in postmortem studies of patients with GAN [4,8].…”

“…Unlikely sometimes, the symptoms and signs of CNS involvement can predominate. It is reported that even if there is no clinical sign of CNS involvement, there may be EEG and MRI abnormalities [6]. Some rare diseases may have to be considered in the differential diagnosis, such as severe early-onset hereditary neuropathies (CMT4A, CMT4B, CMT4C, CMT4E) and infantile neuroaxonal dystrophy, which has more evidence of cerebral involvement and more scattered lesions in the peripheral nerves differing, especially on ultramicroscopic examination, in their pathological appearance.…”

Diagnosis and Pathogenesis of Late-Onset Genetic Metabolic Encephaloneuromyopathies

“…Neuro metabolic diseases can therefore be classified in relation to their different cellular and subcellular pathogenesis which may be secondary to: (a) Changes in the internal compartment of the cells with storage of substances that can be toxic for the cells (some lysosomal diseases, ceroid lipofuscinoses) [31]; (b) diseases with changes in molecu lar structure and functions of cell membranes (several lipidoses, glycoproteinoses, gangliosidoses) [32,33]; (c) diseases with alterations in cell energy metabolism (mito chondrial diseases) [10]; (d) diseases with cytoskeletal abnormalities (Alzheimer's disease, giant axon neuropa thy) [34][35][36][37]; (e) diseases with alterations in the mecha nisms of DNA repair (ataxia telangiectasia of Louis Bar; xeroderma pigmentosum) [5]. As far as the pathogenesis of the apparent selectivity of the lesions for certain types of nervous system cells is concerned, there are a number of hypotheses, none of which however has yet been con firmed by experimental data.…”