Confirmation of mutations inPROSCas a novel cause of vitamin B 6 -dependent epilepsy

Plecko B, Zweier M, Begemann A, Mathis D, Schmitt B, Striano P, Baethmann M, Vari MS, Beccaria F, Zara F, Crowther LM, Joset P, Sticht H, Papuc SM, Rauch A (2017)

Publication Type: Journal article

Publication year: 2017


Book Volume: 54

Pages Range: 809-814

Journal Issue: 12

DOI: 10.1136/jmedgenet-2017-104521


Vitamin-B6-dependent epilepsies are a heterogenous group of treatable disorders due to mutations in several genes (ALDH7A1, PNPO, ALPLorALDH4A1). In neonatal seizures, defects inALDH7A1 and PNPOexplain a major fraction of cases. Very recently biallelic mutations inPROSCwere 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 B6plasma profiles on pyridoxine did not enable the differentiation of patients withPROSCmutations. 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 withPROSCmutations was indistinguishable fromALDH7A1andPNPOdeficiency. We therefore confirmPROSCas a novel gene for vitamin-B6-dependent epilepsy and delineate a non-specific plasma vitamin B6profile under pyridoxine treatment.

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Plecko, B., Zweier, M., Begemann, A., Mathis, D., Schmitt, B., Striano, P.,... Rauch, A. (2017). Confirmation of mutations inPROSCas a novel cause of vitamin B 6 -dependent epilepsy. Journal of Medical Genetics, 54(12), 809-814.


Plecko, Barbara, et al. "Confirmation of mutations inPROSCas a novel cause of vitamin B 6 -dependent epilepsy." Journal of Medical Genetics 54.12 (2017): 809-814.

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