The pattern of inheritance in this entire group of diseases, as already stated, is probably autosomal recessive. Diagnostic methods applicable to amniotic fluid and cells are being developed so that prenatal diagnosis will be possible, prompted often by the occurrence of the disease in an earlier child. Neurons are vacuolated rather than stuffed with granules, much like the lymphocytes and liver cells. The specific biochemical abnormalities, as far as they are known, are listed in Table 36-3. There is no specific treatment although bone marrow transplantation has been investigated.
This disorder is probably inherited as an autosomal recessive trait. The onset is in late infancy, after apparently normal earlier development. The main clinical findings are stunting of growth, evident by the second and third years; photosensitivity of the skin; microcephaly; retinitis pigmentosa, cataracts, blindness, and pendular nystagmus; nerve deafness; delayed psychomotor and speech development; spastic weakness and ataxia of limbs and gait; occasionally athetosis; amyotrophy with abolished reflexes and reduced nerve conduction velocities; wizened face, sunken eyes, prominent nose, prognathism, anhidrosis, and poor lacrimation (resembling progeria and bird-headed dwarfism). Some cases show calcification of the basal ganglia. The CSF is normal, and there are no diagnostic biochemical findings.
Pathologic examination reveals a small brain, striatal and cerebellar calcifications, leukodystrophy like that of Pelizaeus-Merzbacher disease, and a severe cerebellar cortical atrophy. The peripheral nerve changes are those of a primary segmental demyelination.
It is now apparent that Cockayne syndrome, like ataxia-telangiectasia, is a consequence of mutations in genes that mediate DNA repair. At least three different forms of Cockayne syndrome have been identified, each with a different underlying mutation.
Other Metabolic Diseases of Late Infancy and Early Childhood
Globoid cell leukodystrophy (Krabbe), subacute necrotizing encephalomyelopathy (Leigh), and Gaucher disease may also begin in late infancy or early childhood. They are described in the preceding section of this chapter. Familial striatocerebellar calcification (Fahr disease) and Lesch-Nyhan disease may also become manifest in this age period, but they usually have a later onset and are therefore described with the diseases of later childhood in the section that follows.