In type 2 or so-called juvenile GM1 gangliosidosis, the onset is between 12 and 24 months, with survival for 3 to 10 years. The first sign is usually difficulty in walking, with frequent falls, followed by awkwardness of arm movements, loss of speech, severe mental regression, gradual development of spastic quadriparesis and pseudobulbar palsy (dysarthria, dysphagia, drooling), and seizures. Retinal changes are variable—usually they are absent—but macular red spots may be seen at the age of 10 to 12 years; vision is usually retained, but strabiusmus is common. There is a facial dysmorphism resembling that of the Hurler syndrome, and the liver and spleen are enlarged. Important laboratory findings are hypoplasia of the thoracolumbar vertebral bodies, mild hypoplasia of the acetabula, and the presence in the bone marrow of histiocytes with clear vacuoles or wrinkled cytoplasm. As noted in the discussion of Tay-Sachs disease, leukocytes and cultured skin fibroblasts show a deficiency or absence of beta-galactosidase activity. GM1 ganglioside accumulates in the cerebral neurons.
Although not strictly speaking, a metabolic disturbance, under this title, Kinsbourne described a form of widespread, continuous myoclonus (except during deep sleep) affecting male and female infants whose development had been normal until the onset of the disease at the age of 9 to 20 months. It is therefore referable to the other forms of childhood and infantile myoclonus as discussed in
Chap. 30 with paraneoplastic disorders. The myoclonus evolves over a week or less, affects all the muscles of the body, and interferes seriously with all the natural muscular activities of the child. The eyes are notably affected by rapid (up to 8/s), irregular conjugate movements (“dancing eyes” of an opsoclonic type). The child is irritable and speech may cease. All laboratory tests are normal.
Treatment Dexamethasone in doses of 1.5 to 4.0 mg/d suppresses the myoclonus and permits developmental progress. Some patients have recovered from the myoclonus but have been left mentally slow and mildly ataxic. Others have required corticosteroid therapy for 5 to 10 years, with relapse whenever it was discontinued. Ordinary anticonvulsants seem to have no effect. The pathology has not been determined.
A similar syndrome has been observed in conjunction with neuroblastoma in children and as a transient illness of unknown cause (probably viral or postinfectious) in young adults (Baringer et al). A similar condition is also known in adults as a paraneoplastic disease with ovarian, breast, gastric, and bronchogenic carcinomas and with other occult tumors.
In a broader survey of the pediatric opsoclonus-myoclonus syndrome, Pranzatelli and associates reported their experience with 27 cases, some with neural crest tumors, others with viral infections or hypoxic injury (intention myoclonus). In nearly all of their patients there was cerebellar ataxia and mental disorder, and 10 percent had seizures. The CSF was normal. The investigators have emphasized the pathogenetic heterogeneity and defined a rare serotoninergic type (low levels of 5-hydroxytryptophan and homovanillic acid in the CSF) that responds to 5-hydroxyindole acetic acid.
The Neuronal Ceroid Lipofuscinoses (“Batten Disease,” CLN, TPP1, PTT1 Mutations)