Neuronal Ceroid Lipofuscinoses (Batten Disease)

The ceroid lipofuscinoses are autosomal recessive disorders that have been subdivided according to the age at which the neurologic symptoms first appear. The clinical features of these various types are detailed in Table 4.6. These disorders must be considered in the differential diagnosis in the infant or child who develops seizures, loss of acquired milestones, progressive intellectual deterioration, and progressive visual impairment. Confirmation of the diagnosis previously required electron microscopic examination of suitable specimens derived from skin, conjunctiva, muscle, or rectal biopsy that demonstrate characteristic storage materials. It is now more quickly and definitively established by genetic testing for mutations in the CLN3 genes.296,297 No enzymatic deficiency has been identified. Neuroimaging studies reveal nonspecific changes, but are helpful in distinguishing the lipofuscinoses from the various leukodystrophies in which there are striking abnormalities of the white matter.

Juvenile Batten disease (Spielmeyer–Vogt disease) is of particular importance to the ophthalmologist because visual impairment is commonly the presenting symptom (Table 4.6).816 In contrast, the infantile and late infantile forms show a rapidly progressive downhill course and are rarely diagnosed by the ophthalmologist.

Familial Dysautonomia (Riley–Day Syndrome)

This is an autosomal recessive disorder that is confined to Ashkenazi Jews. Although the name suggests that the disorder is strictly one of autonomic dysfunction, the peripheral sensory and motor nerves as well as other neuronal populations are affected.

Children present with poor suck reflex, hypotonia, hypothermia, and nursing difficulties with frequent regurgitation, at birth. Patients with this syndrome also show poor

Table 4.6  Clinical features of the neuronal ceroid lipofuscinoses

temperature control, motor incoordination, reduced deep tendon reflexes, postural hypotension, and emotional lability. The children lack the fungiform papillae on the tongue and have markedly diminished taste sensation.

The most prominent ophthalmological findings are pronounced corneal hypesthesia and absent tears, which in combination lead to corneal ulcerations. Other findings include retinal vascular tortuosity, ptosis, anisocoria, exotropia, and increased incidence of myopia. Optic atrophy has been rarely reported.204 Rizzo et al727 reported three patients with the syndrome who showed visual impairment due to optic atrophy, initially diagnosed after the first decade. The authors suggested that the presence of an optic atrophy demonstrates that there is some degree of CNS involvement in familial dysautonomia.

Infantile Neuroaxonal Dystrophy

Infantile neuroaxonal dystrophy is an autosomal recessive disorder that presents in infancy with psychomotor retardation, truncal hypotonia, peripheral spasticity, and areflexia.327,918 Optic atrophy develops in 40% of cases by 3 years of age.11,257 In one study,247 after 2 years of age, patients show characteristic electroencephalographic changes with fast phase activity superimposed upon a slow background.918 MR imaging showed cerebellar atrophy and mildly increased signal from the cerebellar cortex on T2-weighted images, and a few showed increased signal from the dentate nuclei and from the posterior periventricular white matter. Histopathologically, patients with this disorder have eosinophilic spheroids in the central, peripheral, and autonomic nervous systems; cerebellar degeneration and degeneration of various neuronal, myelin, and glial elements.913 Similar pathologic findings occur in pantothenate kinase-associated neurodegeneration, an autosomal-recessive disorder with a later onset that is more insidiously progressive.305 There is no effective treatment.