Investigators at Queen Mary Hospital, Hong Kong, report a case of Ohtahara syndrome with transient folinic acid responsiveness but without evidence of antiquitin dysfunction in a girl later found to have a known STXBP1 mutation. At day 3 of life she had a cluster of epileptic spasms lasting less than 2 min. Ultrasound showed grade 1 intraventricular hemorrhage, but MRI was normal. EEG showed electrographic seizures from both frontal and anterior temporal regions without clinical seizures, unresponsive to 100mg iv pyridoxine. Seizures were controlled with phenobarbital. At day 70, the infant presented with clusters of flexion or extension epileptic spasms with generalized myoclonic seizures not related to sleep. EEG showed burst suppression pattern, refractory to medication and typical of Ohtahara syndrome. Seizures were unresponsive to pyridoxal phosphate and AEDs. Finally, folinic acid 5 mg/kg per day was added with dramatic response. The child was seizure-free in 1 day, and the EEG showing only generalized slowing had no burst-suppression pattern 4 days later. She was seizure-free for 6 months but relapsed at 10 months of age during a febrile illness. Seizures were finally controlled with sodium valproate and clobazam, but she had severe global developmental delay. Mutation analysis of the ALDH7A1 (antiquitin) gene was negative. Mutation screening revealed a missense mutation in exon 16 of the STXBP1 gene. Analysis of parental DNA confirmed the mutation as de novo. [1]

COMMENTARY. In addition to Ohtahara syndrome, STXBP1 mutations are associated with West syndrome, and learning disabilities. For Ohtahara syndrome caused by STXBP1 mutations, a trial of folinic acid is indicated. Folinic acid responsive seizures are identical to pyridoxine-dependent epilepsy, and both are caused by a-AASA dehydrogenase deficiency with mutations in the ALDH7A1 (antiquitin) gene [2]. Two patients with neonatal epileptic encephalopathy are reported whose CSF showed the marker of folinic acid-responsive seizures, but who responded to pyridoxine [2]. Treatment with both pyridoxine and folinic acid is recommended for infants with alpha-AASA dehydrogenase deficiency. The Hong Kong patient's seizures caused by mutations in the STXBP1 gene showed transient folinic acid responsiveness and no response to pyridoxine.