PT - JOURNAL ARTICLE AU - Barbara Plecko AU - Markus Zweier AU - Anaïs Begemann AU - Deborah Mathis AU - Bernhard Schmitt AU - Pasquale Striano AU - Martina Baethmann AU - Maria Stella Vari AU - Francesca Beccaria AU - Federico Zara AU - Lisa M Crowther AU - Pascal Joset AU - Heinrich Sticht AU - Sorina Mihaela Papuc AU - Anita Rauch TI - Confirmation of mutations in <em>PROSC</em> as a novel cause of vitamin B<sub> <sub>6</sub> </sub>-dependent epilepsy AID - 10.1136/jmedgenet-2017-104521 DP - 2017 Dec 01 TA - Journal of Medical Genetics PG - 809--814 VI - 54 IP - 12 4099 - http://jmg.bmj.com/content/54/12/809.short 4100 - http://jmg.bmj.com/content/54/12/809.full SO - J Med Genet2017 Dec 01; 54 AB - Vitamin-B6-dependent epilepsies are a heterogenous group of treatable disorders due to mutations in several genes (ALDH7A1, PNPO, ALPL or ALDH4A1). In neonatal seizures, defects in ALDH7A1 and PNPO explain a major fraction of cases. Very recently biallelic mutations in PROSC were shown to be a novel cause in five families. We identified four further unrelated patients harbouring a total of six different mutations, including four novel disease mutations. Vitamin B6 plasma profiles on pyridoxine did not enable the differentiation of patients with PROSC mutations. All four patients were normocephalic and had normal cranial imaging. Pyridoxine monotherapy allowed complete seizure control in one, while two patients had occasional febrile or afebrile seizures and one needed additional valproate therapy for photosensitive seizures. Two patients underwent a controlled pyridoxine withdrawal with signs of encephalopathy within a couple of days. Three had favourable outcome with normal intellectual properties at age 12.5, 15.5 and 30 years, respectively, while one child had marked developmental delay at age 27 months. The clinical and electroencephalographic phenotype in patients with PROSC mutations was indistinguishable from ALDH7A1 and PNPO deficiency. We therefore confirm PROSC as a novel gene for vitamin-B6-dependent epilepsy and delineate a non-specific plasma vitamin B6 profile under pyridoxine treatment.