Epilepsy in inherited metabolic disorders

The study of neurometabolic diseases is still in a prolonged preliminary stage. The catalogue of these diseases continues to grow; some known clinical syndromes have been subdivided into a number of variants once the genes that cause them have been identified, and at the same time new metabolic disorders have been discovered that aggravate or contribute to forms of epilepsy not previously classified as cerebral metabolic disorders.

This review presents the basic principles underlying the recognition and treatment of epilepsy caused by neurometabolic diseases. These disorders are divided (purely for the sake of convenience) into epilepsy presenting in newborn infants, children, and adolescents and adults, recognizing that there is a significant degree of overlap between these chronological stages. Current analytical methods and therapeutic approaches are summarized both from a general point of view and within the context of each clinical syndrome, acknowledging that each patient presents specific peculiarities and that, in general, antiepileptic drugs provide few benefits compared with more specific types of therapy (eg, special diets or vitamins) when indicated. We also include therapeutic recommendations and a general approach to fulminant epilepsies of neurometabolic origin, emphasizing the importance of identifying all of the proband's relatives who may be potential carriers of a genetic disorder during the diagnostic and genetic counselling process. Particular emphasis is placed on disorders for which there is curative treatment and on the importance of follow-up by expert professionals.

It is expected that in a few years' time it will be possible to know the metabolomic profile of these diseases (possibly by non-invasive methods), thus facilitating accurate diagnosis and making it possible to establish the response to treatment and to identify all individuals who are carriers or remain minimally symptomatic in terms of their risk of manifesting or transmitting epilepsy.