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
Journal
Book Volume: 54
Pages Range: 809-814
Journal Issue: 12
DOI: 10.1136/jmedgenet-2017-104521
Abstract
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.
Authors with CRIS profile
Involved external institutions
Universitäts-Kinderspital Zürich
Switzerland (CH)
University of Zurich / Universität Zürich (UZH)
Switzerland (CH)
University of Genova / Università degli Studi di Genova
Italy (IT)
Klinikum Dritter Orden
Germany (DE)
Hospital Carlo Poma
Italy (IT)
Switzerland (CH)
University of Zurich / Universität Zürich (UZH)
Switzerland (CH)
University of Genova / Università degli Studi di Genova
Italy (IT)
Klinikum Dritter Orden
Germany (DE)
Hospital Carlo Poma
Italy (IT)
How to cite
APA:
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. https://doi.org/10.1136/jmedgenet-2017-104521
MLA:
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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