Jen et al. (2005) reported a 10-year-old boy with a severe form of episodic ataxia with seizures, migraine, and alternating hemiplegia. From birth, he had experienced 4 discrete episodes of ataxia and slurred speech, seemingly triggered by febrile ... Jen et al. (2005) reported a 10-year-old boy with a severe form of episodic ataxia with seizures, migraine, and alternating hemiplegia. From birth, he had experienced 4 discrete episodes of ataxia and slurred speech, seemingly triggered by febrile illness. At age 6 years, he developed a severe right-sided headache followed by hemiparesis and decreased consciousness lasting 5 days. MRI showed cerebellar atrophy, and neurologic examination showed mild interictal truncal ataxia. De Vries et al. (2009) reported a Dutch family in which 3 individuals had episodic ataxia. The phenotype was milder than that described by Jen et al. (2005). Onset was in the first or second decade. Episodic attacks lasted 2 to 3 hours and were often associated with nausea, vomiting, photophobia, phonophobia, vertigo, diplopia, and/or slurred speech. Headaches were not a prominent feature. Attacks were provoked by emotional stress, fatigue, or consumption of alcohol or caffeine. The 35-year-old proband noted that truncal and gait ataxia during the attacks became more prominent with age. The proband had interictal horizontal gaze-evoked nystagmus without gait or truncal ataxia. All patients showed a favorable response to treatment with acetazolamide.
In a 10-year-old boy with EA6, Jen et al. (2005) identified a heterozygous mutation in the SLC1A3 gene (600111.0001). Cellular studies showed that the mutation resulted in markedly decreased glutamate uptake. Jen et al. (2005) postulated a role ... In a 10-year-old boy with EA6, Jen et al. (2005) identified a heterozygous mutation in the SLC1A3 gene (600111.0001). Cellular studies showed that the mutation resulted in markedly decreased glutamate uptake. Jen et al. (2005) postulated a role for abnormal glutamate transmission in the neurologic features seen in this patient. In 3 affected members of a family with EA6, de Vries et al. (2009) identified a heterozygous mutation in the SLC1A3 gene (600111.0002). There was 1 unaffected carrier of the mutation, indicating reduced penetrance. Functional expression studies showed that the mutation resulted in an 18% decrease in glutamate uptake, which was not as severe as that observed with the mutation reported by Jen et al. (2005). De Vries et al. (2009) concluded that EA6 symptoms were correlated with the extent of glutamate transporter dysfunction.