J Med Genet 2017 12 8;54(12):809-814. Epub 2017 Apr 8.
radiz - "Rare Disease Initiative Zurich, Clinical Research Priority Program for Rare Diseases University of Zurich", University of Zurich, Zurich, Switzerland.
Vitamin-B-dependent epilepsies are a heterogenous group of treatable disorders due to mutations in several genes ( or ). In neonatal seizures, defects in explain a major fraction of cases. Very recently biallelic mutations in 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 B plasma profiles on pyridoxine did not enable the differentiation of patients with 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 mutations was indistinguishable from and deficiency. We therefore confirm as a novel gene for vitamin-B-dependent epilepsy and delineate a non-specific plasma vitamin B profile under pyridoxine treatment.