Once a neurologic syndrome is clearly established, there is a particular advantage in determining whether its main characteristics reflect a disorder of the cerebral white matter (oligodendrocytes and myelin) or of gray matter (neurons). Indicative of predominantly white matter affection (leukodystrophy or leukoencephalopathy) are early onset of spastic paralysis of the limbs, with or without ataxia, and visual impairment with optic atrophy but normal retinae. Seizures and intellectual deterioration are late events. MRI usually confirms the involvement of white matter. Indicative of gray matter disease (poliodystrophy or polioencephalopathy) are the early onset of seizures, myoclonus, blindness with retinal changes, and mental regression. Choreoathetosis and ataxia, spastic paralysis, and signs of sensorimotor tract involvement occur later. On MRI, only a generalized atrophy and ventricular enlargement may be seen.
Neuronal storage diseases, such as those described in the previous section, as well as neuroaxonal dystrophy and the lipofuscinoses, conform to the pattern of gray matter diseases (see Table 36-5). Metachromatic leukodystrophy, globoid-cell (Krabbe) disease, sudanophilic leukodystrophy, and spongy degeneration of infancy (Canavan disease) exemplify white matter diseases (see Table 36-6). Although this mode of categorization is helpful, there is some degree of overlap; for example, Tay-Sachs disease, a poliodystrophy, also causes white matter changes, and metachromatic leukodystrophy may be accompanied by some degree of neuronal storage.
The following are inherited metabolic diseases that become evident clinically in late infancy and early childhood: 1. Many of the milder disorders of amino acid metabolism 2. Metachromatic and other leukodystrophies 3. Late infantile GM1 gangliosidosis 4. Late infantile Gaucher disease and Niemann-Pick disease 5. Neuroaxonal dystrophy 6. The mucopolysaccharidoses 7. The mucolipidoses 8. Fucosidosis 9. The mannosidoses 10. Aspartylglycosaminuria 11. Ceroid lipofuscinosis (Jansky-Bielschowsky disease) 12. Cockayne syndrome
The Aminoacidopathies (Aminoacidurias)
In a group of 48 inherited aminoacidopathies tabulated by Rosenberg and Scriver, at least one-half were associated with recognizable neurologic abnormalities. Twenty other aminoacidopathies result in a defect in the renal transport of amino acids, some of which secondarily damage the nervous system. Usually, when the nervous system is involved, the only clinical manifestation is simply a lag in psychomotor development, which, if mild, does not become apparent until the second and third years or later. Like other inherited metabolic disorders, the aminoacidurias do not impair growth, development, or maturation in utero or interfere with parturition. (This is the result of the maternal blood supply, which defines the amino acid balance in utero.) No physical sign betrays their presence in the early months of life. The only possible means of detection is by the screening of all newborns. Table 36-1 indicates the relative frequency of these diseases and Table 36-2 summarizes the practical tests for their identification.