Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
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.
Confirmation of mutations in PROSC as a novel cause of vitamin B 6 -dependent epilepsy.
J Med Genet. 2017; 54(12): 809-814.
Doi: 10.1136/jmedgenet-2017-104521
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- Führende Autor*innen der Med Uni Graz
- Plecko Barbara
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- Abstract:
- 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. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
- Find related publications in this database (using NLM MeSH Indexing)
- Adolescent -
- Adult -
- Alleles -
- Child -
- Child, Preschool -
- Consanguinity -
- DNA Mutational Analysis -
- Electroencephalography -
- Epilepsy - diagnosis
- Epilepsy - drug therapy
- Epilepsy - etiology
- Epilepsy - metabolism
- Female -
- Gene Frequency -
- Genetic Association Studies -
- Genetic Predisposition to Disease -
- Genotype -
- Humans -
- Male -
- Mutation -
- Phenotype -
- Proteins - genetics
- Pyridoxine - therapeutic use
- Vitamin B 6 - blood
- Vitamin B 6 - metabolism