Consensus guidelines for the diagnosis and management of pyridoxine-dependent epilepsy due to α-aminoadipic semialdehyde dehydrogenase deficiency.

Pyridoxine-dependent epilepsy (PDE-ALDH7A1) is an autosomal recessive condition due to a deficiency of α-aminoadipic semialdehyde dehydrogenase, which is a key enzyme in lysine oxidation. PDE-ALDH7A1 is a developmental and epileptic encephalopathy that was historically and empirically treated with pharmacologic doses of pyridoxine. Despite adequate seizure control, most patients with PDE-ALDH7A1 were reported to have developmental delay and intellectual disability. To improve outcome, a lysine-restricted diet and competitive inhibition of lysine transport through the use of pharmacologic doses of arginine have been recommended as an adjunct therapy. These lysine-reduction therapies have resulted in improved biochemical parameters and cognitive development in many but not all patients. The goal of these consensus guidelines is to re-evaluate and update the two previously published recommendations for diagnosis, treatment, and follow-up of patients with PDE-ALDH7A1. Members of the International PDE Consortium initiated evidence and consensus-based process to review previous recommendations, new research findings, and relevant clinical aspects of PDE-ALDH7A1. The guideline development group included pediatric neurologists, biochemical geneticists, clinical geneticists, laboratory scientists, and metabolic dieticians representing 29 institutions from 16 countries. Consensus guidelines for the diagnosis and management of patients with PDE-ALDH7A1 are provided.

Symptoms of narcolepsy in children misinterpreted as epilepsy.

Differentiating an epileptic seizure from some other paroxysmal event is a common challenge in clinical practice. Many paroxysmal events mimic epileptic seizures and misdiagnosis can have disastrous consequences. Incorrectly identifying an event as an epileptic seizure can lead to unnecessary investigations and instigation of inappropriate treatment regimes. We report five patients referred to regional Paediatric Neuroscience Centres for investigation of events initially suspected of being epileptic seizures. All five patients were subsequently diagnosed as having narcolepsy. Suspected diagnoses were absence epilepsy (four patients), generalized epilepsy with astatic seizures (two patients) and focal epileptic seizures (two patients). Diagnostic confusion arose because lack of responsiveness due to excessive sleepiness was mistaken for epileptic absences, and cataplexy was confused with a variety of seizure types. In each case, videotape recording of clinical events aided in making the diagnosis of cataplexy. At presentation, all five children had excessive daytime sleepiness with cataplexy. Following correct diagnosis and appropriate management, an improvement in symptoms was reported in all cases. Narcolepsy/cataplexy should be included in the differential diagnoses of paroxysmal disorders, particularly if there are associated sleep symptoms or behavioural difficulties. It is important to take a sleep history when evaluating any disorder of the central nervous system.