Inherited metabolic epilepsies-established diseases, new approaches.

Abstract

Inherited metabolic epilepsies (IMEs) represent the inherited metabolic disorders (IMDs) in which epilepsy is a prevailing component, often determining other neurodevelopmental outcomes associated with the disorder. The different metabolic pathways affected by individual IMEs are the basis of their rarity and heterogeneity. These characteristics make it particularly challenging to establish their targeted therapies, and many of the IMEs are treated nowadays only symptomatically and supportively. However, owing to immense molecular and genetic progress in the last decades, important features of their pathomechanisms have been elucidated. This has led to advancements in the development of novel diagnostic approaches and specific therapies for a considerable number of these unique disorders. This review provides an overview of the broad approach to the diagnosis and management of IMEs, along with their eminent and new individual treatment options, ranging from dietary therapies and vitamins to enzyme and gene replacement therapies. PLAIN LANGUAGE SUMMARY: Inherited metabolic disorders (IMDs) in which epilepsy is a main symptom are considered inherited metabolic epilepsies (IMEs). It is challenging to develop targeted therapies for IMEs since they are rare and individually different in characteristics. Therefore, many of the IMEs are currently treated only symptomatically. However, scientific progress in the last decades led to the creation of specific treatments for many of these unique disorders. This review provides an overview of the approach to the diagnosis and management of IMEs, including the available newer therapeutic modalities.