These rare forms of inherited metabolic disease are notable for their chronicity and for the prominence, eventually, of a particular neurologic symptom or syndrome. Once the disease is established, however, there is nearly always evidence of involvement of multiple neuronal systems, reflected in a subtle or overt dementia, character disorder, or signs referable to corticospinal, cerebellar, extrapyramidal, visual, and peripheral nerve structures. This multiplicity of neuronal system involvement is much more a feature of heritable metabolic disease than of degenerative disease and the finding of such involvement should provoke a search for an inherited metabolic disorder.
To reiterate the clinical aspects, the aforementioned dictum that tract involvement (corticospinal, cerebellar, peduncular, sensory, optic nerve) indicates a leukodystrophy and that “gray matter” signs (seizures, myoclonus, dementia, retinal lesions) indicate a poliodystrophy is useful mainly in the early stages of a disease. Some of the lysosomal storage diseases affect both galactolipids (galactocerebrosides and sulfatides) and gangliosides; hence both white and gray matters are involved. The paper by Turpin and Baumann is of interest when this group of diseases is viewed from the strictly psychiatric point of view.
Certain outstanding clinical symptoms that are more often attributable to common diseases of the adult nervous system, such as multiple sclerosis and atherosclerosis, are sometimes the result of an inborn error of metabolism. These infrequent instances are categorized by their main features in Table 36-8, which is adopted from Grey et al.
Viewed from another perspective, patients are sometimes referred for the evaluation of diffuse white matter disease of the cerebrum that has been found with aiming studies. Multiple sclerosis and its variants come to mind immediately as noted by Eldridge et al but, as discussed in Chap. 35, diseases other than MS are more likely to cause diffuse, symmetric, and bilateral changes in the deep hemispheres. These include CADASIL, Susac syndrome, infiltrative tumors such as lymphoma and gliomatosis cerebri, and autoimmune systemic conditions that secondarily affect the white matter, perhaps by a mechanism of microvasculitis. However, the dysmyelinating leukodystrophies discussed in this chapter may manifest late in life and enter into the differential diagnosis of this imaging appearance. As a guide to evaluating such cases, Schiffmann and van der Knaap have provided an extensive listing of diseases and characterized them by the presence of the MRI characteristics, particularly the presence of hypomyelination in which the white matter is hyperintense or isointense to the cortex on T1-weighted MRI images (and usually less T2 hyperintense than in other pathologic changes of white matter). They further divide the group that is not hypomyelinated by the feature of confluence of multifocal distribution. The algorithm they provide may guide the clinician in choosing an appropriate laboratory plan.
In concluding this discussion, which classifies the inherited monogenetic metabolic diseases in accordance with their clinical characteristics, the reader will appreciate its artificiality. Nearly every one of the diseases of each category may present some neurologic abnormality other than the ones we have emphasized, so that the potential number of variations is almost limitless. However, the plan presented here of thinking of these diseases in reference to age periods and syndromes, is of heuristic value and facilitates clinical study of this extremely difficult segment of neurologic medicine.