A useful principle in recognizing those adolescents with a metabolic brain disease is that sooner or later, such a condition will cause a regression in cognitive and intellectual functions. Bipolar disease, sociopathies, and character disorders do not result in the loss of neurologic function. The recognition of a metabolic cause of mental deterioration depends on the demonstration of failing memory, impaired thinking, inability to learn, and loss of verbal and arithmetic abilities, many of which are measured quantitatively by intelligence tests. The appearance of pyramidal signs, aphasia, apraxia, ataxia, or areflexia further sets them apart.
If one reviews all the diseases described in this chapter and selects those that may demonstrate regression of cognitive function in association with personality change and alteration of behavior in an adult—diseases that may for a time be unaccompanied by other neurologic abnormalities—the following metabolic disorders merit special consideration in approximate relative order of importance: 1. Wilson disease 2. Adrenoleukodystrophy 3. Metachromatic leukodystrophy 4. PKAN pigmentary degeneration 5. Late-onset neuronal ceroid-lipofuscinosis (Kufs form) 6. Juvenile and adult Gaucher disease (type III) 7. Some of the mucopolysaccharidoses 8. Adult GM2 gangliosidosis 9. Mucolipidosis I (type I sialidosis) 10. Lafora-body myoclonic epilepsy 11. Nonwilsonian copper disorder (hereditary ceruloplasmin deficiency)
In each of these diseases, dementia and personality disorder may gradually develop and exist for many months, even a year or two, before other neurologic signs appear. One must look carefully for the earliest signs of movement disorders and other neurologic abnormalities, which greatly clarify the diagnostic problem. The common use of neuroleptic drugs, causing tardive dyskinesia and parkinsonian signs, is an obstacle to determining if there are neurologic features in these ostensibly psychiatric conditions.
The increasing range and precision of biochemical and cytologic tests have brought to light a number of inherited metabolic diseases that sometimes have their onset in adult life. Such disorders, while uncommon, nevertheless are important because they must be considered in the differential diagnosis of degenerative diseases. Also to be considered in the differential diagnosis is an array of mitochondrial disorders, to be discussed further on in this chapter.
In the last three decades, the authors have personally observed or have otherwise come to know of examples of the following metabolic diseases, the onset of which was in adult life: 1. Metachromatic leukoencephalopathy 2. Adrenoleukodystrophy 3. Globoid body leukodystrophy (Krabbe disease) 4. Kufs form of neuronal ceroid lipofuscinosis 5. GM2 gangliosidosis 6. Wilson disease 7. Gaucher disease 8. Niemann-Pick disease 9. Carnitine palmityl transferase deficiency 10. Mucopolysaccharide encephalopathy 11. Mucolipidosis type I 12. Polyneuropathies (Andrade disease, Fabry disease, porphyria, Refsum disease) 13. Mitochondrial diseases, particularly progressive