The disease becomes manifest clinically in childhood or adolescence, with intermittent lancinating pains and dysesthesias of the extremities. A notable feature of these pains is their evocation by fever, hot weather, and vigorous exercise. Usually there is no sensory loss, but autonomic disturbances have been recorded in a series of our cases. Many years later there is a diffuse vascular involvement that leads to hypertension, renal damage, cardiomegaly, and myocardial ischemia. Thrombotic infarctions occur in the brain during early adult years. Occasional cases are discovered in adulthood with confluent cerebral white matter changes on MRI and progressive problems such as dysarthria.
The characteristic angiokeratomas tend to be most prominent periumbilically and resemble small angiomas that obliterate slightly with pressure. Desnick and colleagues have reviewed the neurologic, neuropathologic, and biochemical findings in this disease, and Cable and colleagues have written informatively on the autonomic aspects.
Treatment Enzyme replacement, given by infusion, is now available. The two main trials of this treatment, summarized in an editorial by Pastores and Thadhani, were each conducted quite differently. Both showed an improvement in kidney and other organ function but only one demonstrated a reduction in neuropathic pain, and neither studied the risk of stroke. Like enzyme replacement therapy for Gaucher disease, prolonged treatment is expensive; but some evidence from the trials cited above indicates that certain aspects of the disease are reversible.
The painful neuropathic features that have brought several cases to our attention are discussed with the polyneuropathies, in Chap. 43.
This disorder was discussed briefly with the neonatal metabolic disorders. The occurrence of stroke as a complication of this disorder was placed on record by our colleagues Shih et al (1977). A child 4.5 years of age, whose development had been retarded since birth (seizures and opisthotonos had been present), became hemiplegic. Another unrelated child, supposedly normal until 2 years of age, entered the hospital with fever, confusion, generalized seizures, right hemiplegia, and aphasia (infantile hemiplegia); subluxation of the lenses (upward) was discovered later. There was an increased level of sulfite and thiosulfate and an abnormal amino acid, S-sulfocysteine, in the blood. One child appeared to respond to a low-sulfur–amino-acid diet.
Certain metabolic diseases may be the cause of serious disturbances of cognitive function and behavior, even in the adolescent and early adult period. The diagnosis and management of these metabolic diseases are so unusual that some special remarks are appropriate. When they present later in adolescence and adult life they evolve more slowly than childhood forms. The most obvious and easily detectable of these derangements are in the cognitive sphere, that is, memory, calculation, problem solving, and verbal skills. Impulsivity, loss of self-control, and antisocial behavior are the most troubling behavioral abnormalities. Each of these phenomena has its own cerebral anatomy, as pointed out in Chap. 21, and the state of dementia comprises various degrees and combinations of these abnormalities.
Intellectual functions are difficult to accurately assess in early childhood. Slowness in learning and in acquiring language functions become manifest in school and may then be interpreted loosely as developmental delay. Up until school age, these intellectual functions have not developed sufficiently to allow recognition of their regressive course. Only in late childhood do they become clearly distinguishable and measurable by standardized tests. Far less tangible are subtle changes in personality and behavior.