Normal and defective neuronal membranes: structure and function: neuronal lesions in peroxisomal disorders.

[neonatal adrenoleukodystrophy]

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 .