Normal and defective neuronal membranes:: Structure and function -: Neuronal lesions in peroxisomal disorders

Neuronal involvement in the peroxisomal disorders is divided into two main groups: developmental and postdevelopmental or degenerative. In the former the major lesions are neuronal migration abnormalities, which vary from severe in the cerebro-hepato-renal (Zellweger) syndrome (ZS) to mild in neonatal adrenoleukodystrophy. More common, but much less severe, are defects in neuronal differentiation or terminal migration, particularly involving the inferior medullary olives. Ultrastructural and neurochemical observations in ZS suggest that the presence of abnormal cytosomes in migrating neurons and radial glia, probably the result of excessive very long chain fatty acids, are responsible in part for its major neocortical migration defect, parasylvian pachygyria-polymicrogyria. The postdevelopmental neuronal lesions involve specialized sensory neurons of the retina and the inner ear, resulting in atypical retinitis pigmentosa and its consequent visual defects and sensorineural hearing deficits. Neuronal atrophy and/or loss is seen in both the dorsal-root ganglia of adrenomyeloneuropathy and the atrophic cerebellum of rhizomelic chondodysplasia punctata. The underlying pathophysiology of these neuronal lesions is postulated to be caused by the incorporation of abnormal fatty acids into neuronal membranes, leading to an unresponsiveness to neurotrophic factors necessary for normal function and survival or to increased permeability of calcium channels and cell death.