Infantile-onset spinocerebellar ataxia (IOSCA) is a severe, progressive neurodegenerative disorder characterized by normal development until age one year, followed by onset of ataxia, muscle hypotonia, loss of deep-tendon reflexes, and athetosis. Ophthalmoplegia and sensorineural deafness develop by age seven years. By adolescence, affected individuals are profoundly deaf and no longer ambulatory; sensory axonal neuropathy, optic atrophy, autonomic nervous system dysfunction, and hypergonadotropic hypogonadism in females become evident. Epilepsy can develop into a serious and often fatal encephalopathy: myoclonic jerks or focal clonic seizures that progress to epilepsia partialis continua followed by status epilepticus with loss of consciousness.
The diagnosis of IOSCA is established in a proband with typical clinical findings and identification of biallelic pathogenic variants in TWNK by molecular genetic testing.
Treatment of manifestations: Hearing loss, sensory axonal neuropathy, ataxia, psychotic behavior, and severe depression are treated in the usual manner. Conventional antiepileptic drugs (phenytoin and phenobarbital) are ineffective in most affected individuals.
Surveillance: Small children: neurologic, audiologic, and ophthalmologic evaluations every six to 12 months; neurophysiologic studies when indicated; brain MRI every three to five years. Adolescents and adults: neurologic examination yearly; audiologic and ophthalmologic examinations every one to two years; EEG and brain MRI at least during status epilepticus.
Agents/circumstances to avoid: Valproate, which can cause significant elevation of serum concentration of bilirubin and liver enzymes.
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