ClinVar

Galimberti et al. (2006) reported a Caucasian boy with mild learning difficulty and seizures treated with valproate therapy at age 8 years. During 2 years of valproate treatment, he showed increased irritability and learning difficulties, worsening sleep and EEG anomalies, and neuropsychologic decline. Brain MRI showed enlargement of the lateral ventricles and cerebral and cerebellar cortical sulci. At age 10 years, discontinuation of valproate led to clinical improvement over 3 months. Genetic analysis detected a heteroplasmic 8383C-T transition in the MTATP8 gene, resulting in a pro-to-ser substitution, in the boy, his unaffected mother and grandmother, and in a maternal uncle with rare generalized seizures who was not exposed to valproate. Galimberti et al. (2006) noted that Lam et al. (1997) had reported another patient with encephalopathy triggered by valproate therapy who was found to have a mutation in the MTTL1 gene (590050.0001).