Metabolic Brain Disease

, Volume 33, Issue 6, pp 1781–1786 | Cite as

Contemporary scope of inborn errors of metabolism involving epilepsy or seizures

  • Birutė Tumienė
  • Borut Peterlin
  • Aleš Maver
  • Algirdas Utkus
Review Article


Many inborn errors of metabolism may present with epilepsy or seizures, however, current scope of these diseases is unknown. Due to available precision medicine approaches in many inborn errors of metabolism and sophisticated traditional diagnostics, this group of disorders is of special relevance to clinicians. Besides, as current treatment is challenging and unsuccessful in more than 30% of all epilepsy patients, these diseases may provide valuable models for ictogenesis and epileptogenesis studies and potentially pave the ways to identification of novel treatments. The aim of this study was to elucidate genetic architecture of inborn errors of metabolism involving epilepsy or seizures and to evaluate their diagnostic approaches. After extensive search, 880 human genes were identified with a considerable part, 373 genes (42%), associated with inborn errors of metabolism. The most numerous group comprised disorders of energy metabolism (115, 31% of all inborn errors of metabolism). A substantial number of these diseases (26%, 97/373) have established specific treatments, therefore timely diagnosis comes as an obligation. Highly heterogenous, overlapping and non-specific phenotypes in most of inborn errors of metabolism presenting with epilepsy or seizures usually preclude phenotype-driven diagnostics. Besides, as traditional diagnostics involves a range of specialized metabolic tests with low diagnostic yields and is generally inefficient and lengthy, next-generation sequencing-based methods were proposed as a cost-efficient one-step way to shorten “diagnostic odyssey”. Extensive list of 373 epilepsy- or seizures-associated inborn errors of metabolism genes may be of value in development of gene panels and as a tool for variants’ filtration.


Metabolic epilepsy Next-generation sequencing Inherited metabolic disease Diagnostics 


Compliance with ethical standards

Not applicable. This article does not contain any studies with human or animal subjects performed by the any of the authors.

Supplementary material

11011_2018_288_MOESM1_ESM.docx (90 kb)
ESM 1 (DOCX 89 kb)


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of Biomedical Sciences, Faculty of MedicineVilnius UniversityVilniusLithuania
  2. 2.Vilnius University Hospital Santaros KlinikosVilniusLithuania
  3. 3.Clinical Institute for Medical Genetics, Division of GynecologyUniversity of Ljubljana Medical CentreLjubljanaSlovenia

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