This review represents an examination of four groups of neurodegenerative diseases, namely the sphingolipidoses, the adrenoleukodystrophy complex, the neuronal ceroid lipofuscinoses, and the sialidoses/sialuria complex. Using a combination of clinical assessment, neuroradiologic appearance, and clinical neurophysiology, one may develop strategies that lead to specific chemical or biochemical determinations for specific diagnoses. In general, disorders of white matter may be distinguished from disorders of gray matter by their appearance on computed tomography and by abnormalities of nerve conduction velocities and auditory brain stem responses. In contrast, disorders of gray matter may be distinguished from disorders of white matter by their appearance on computed tomography and utilization of electroretinography, visual evoked responses, and, to a lesser extent, EEG findings. Where necessary, skin, conjunctival, or nerve biopsy may prove to be useful adjuncts to the diagnosis. Presently, treatment depends on prevention, although aggressive efforts are under way to establish corrective therapy by enzyme replacement. To this end, the use of already existing animal models may prove to be helpful. (j Child Neurol 1987;2:82-97). © 1987, Sage Publications. All rights reserved.