Objective: To describe a new phenotype and the diagnostic workup of a vitamin-B6-dependent epilepsy due to PLPBP deficiency in an infant with early-onset epilepsy at age 5 ½ months. Methods: Following immediate and impressive clinical response to treatment with pyridoxine, metabolic screening for vitamin-B6-dependent epilepsies and targeted next generation sequencing (NGS) - based gene panel analysis were performed. Potentially pathogenic variants were confirmed by Sanger sequencing in the patient and variants were analyzed in both parents to confirm bi-allelic inheritance. The clinical phenotype and course of disease were compared to the 44 cases reported in the literature, harboring variants in PLPHP and with cases of vitamin-B6-dependent epilepsy due to other known causative genes. Results: levels of alpha-aminoadipic-semialdehyde in urine and amino acids were normal. Two inherited pathogenic variations in PLPHP were found in compound heterozygosity, including one novel deletion. Conclusions: We here describe a previously unreported individual harboring bi-allelic pathogenic PLPHP variants presenting with paroxysmal eye-head-movements followed by epileptic spasms and an almost normal interictal electroencephalogram (EEG), thus expanding the clinical spectrum of PLPBP deficiency. This warrants consideration of vitamin-B6-dependent epilepsies in patients with early-onset epilepsy, including epileptic spasms, and eye movement disorders also beyond the neonatal period even when metabolic screening for vitamin-B6- dependent epilepsies is negative. PLPHP should be included systematically in NGS epilepsy gene panels.

No abstract