RT Journal Article
SR Electronic
T1 Confirmation of mutations in PROSC as a novel cause of vitamin B
6
-dependent epilepsy
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 809
OP 814
DO 10.1136/jmedgenet-2017-104521
VO 54
IS 12
A1 Plecko, Barbara
A1 Zweier, Markus
A1 Begemann, Anaïs
A1 Mathis, Deborah
A1 Schmitt, Bernhard
A1 Striano, Pasquale
A1 Baethmann, Martina
A1 Vari, Maria Stella
A1 Beccaria, Francesca
A1 Zara, Federico
A1 Crowther, Lisa M
A1 Joset, Pascal
A1 Sticht, Heinrich
A1 Papuc, Sorina Mihaela
A1 Rauch, Anita
YR 2017
UL http://jmg.bmj.com/content/54/12/809.abstract
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.