Neuropediatrics 2019; 50(S 02): S1-S55
DOI: 10.1055/s-0039-1698223
Poster Presentations
Poster Area GNP Epilepsy 2
Georg Thieme Verlag KG Stuttgart · New York

Late Diagnosis of Pyridoxine-dependent Epilepsy due to a PROSC-mutation with Whole-exome-Sequencing and Natural History without Administration of Pyridoxine until Adolescence

Authors

  • Katharina Hermann

    1   Universitätsklinikum Hamburg-Eppendorf, Neuropädiatrie, Hamburg, Germany

  • Jessika Johannsen

    2   Universitätsklinikum Hamburg-Eppendorf, Klinik für Kinder- und Jugendmedizin, Neuropädiatrie, Hamburg, Germany

  • Katja Kloth

    3   Universitätsklinikum Hamburg-Eppendorf, Institut für Humangenetik, Hamburg, Germany

  • Jonas Denecke

    2   Universitätsklinikum Hamburg-Eppendorf, Klinik für Kinder- und Jugendmedizin, Neuropädiatrie, Hamburg, Germany
Further Information

Publication History

Publication Date:
11 September 2019 (online)

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    Question: Pyridoxin-dependent epilepsy is a well-known and therapeutically relevant differential diagnosis in seizures of the newborn. Several causal mutations and subsequent metabolic changes are described in the literature, the most frequent underlying cause is an Antiquitin-mutation. In 2016 PROSC-gene mutations were identified as a novel cause of Vitamin B6-responsive epilepsy, not related to a metabolic biomarker. So far 15 patients were reported. We present a further 16-year old patient with a PROSC-mutation with deteriorating seizures and no previous pyridoxine treatment in his medical history.

    Material and Methods: In the clinical workup of the 16 years old male patient with epilepsy onset during his neonatal period and now severe detoriation of seizures with refractory status epilepticus and psychiatric symptoms electroencephalographic phenotype, cranial MRI and metabolic examinations did not lead to a causal diagnosis. Trio whole-exome-sequencing of the patient and his parent was performed and revealed a homozygous PROSC-mutation. With administration of pyridoxine seizures und psychiatric symptoms immediately improved.

    Results: Administration of pyridoxine immediately was initiated, starting intravenously in the intensive care unit, and resulted in substantially and permanently improved epilepsy.

    Discussion: Whereas the administration of pyridoxine in case of neonatal seizures that are not responsive to conventional antiepileptic drugs is common, Vitamin B6-dependet epilepsy might not be considered in older children. Making diagnosis is compounded by missing biomarkers in patients with PROSC-mutation. Therefore the administration of pyridoxine at any age in epilepsies of unknown cause should be considered and genetic testing should be performed.

    Conclusion: With this case report we would suggest to consider a pyridoxin-dependent epilepsies and initiate correspondingly diagnostics and treatment even in older children with epilepsies of unknown cause.


     

    No conflict of interest has been declared by the author(s).