2022 Overview of Metabolic Epilepsies

Abstract

Understanding the genetic architecture of metabolic epilepsies is of paramount importance, both to current clinical practice and for the identification of further research directions. The main goals of our study were to identify the scope of metabolic epilepsies and to investigate their clinical presentation, diagnostic approaches and treatments. The International Classification of Inherited Metabolic Disorders and IEMbase were used as a basis for the identification and classification of metabolic epilepsies. Six hundred metabolic epilepsies have been identified, accounting for as much as 37% of all currently described inherited metabolic diseases (IMD). Epilepsy is a particularly common symptom in disorders of energy metabolism, congenital disorders of glycosylation, neurotransmitter disorders, disorders of the synaptic vesicle cycle and some other IMDs. Seizures in metabolic epilepsies may present variably, and most of these disorders are complex and multisystem. Abnormalities in routine laboratory tests and/or metabolic testing may be identified in 70% of all metabolic epilepsies, but in many cases they are non-specific. In total, 111 metabolic epilepsies (18% of all) have specific treatments that may significantly change health outcomes if diagnosed in time. Although metabolic epilepsies comprise an important and significant group of disorders, their real scope and frequency may have been underestimated.

Prevalence, Clinic-Etiological Spectrum and Outcome of Pediatric Metabolic Epilepsy – A Single Centre Experience

“…However, metabolic epilepsies are more frequently associated with generalized seizures. [ 12 ] We observed that generalized seizures were the dominant semiology that occurred in nearly three-fourth of our cases. Multiple seizure types were noticed in one-third of cases (20/63) which provided a clue to metabolic etiology and further workup.…”

“…The prevalence of epilepsy among inherited metabolic disorders was found to be 40.4% (63/156) in our cohort, which is compatible with previous studies. [ 11 , 12 ] Youssef-Turki et al . [ 13 ] in a recent review have reported that 600 metabolic epilepsies have been identified, accounting for as much as 37% of all currently described inherited metabolic diseases.…”

“…Tumiene et al . [ 12 ] have reported that 66% of metabolic epilepsies are associated with developmental delay.…”

Epilepsy and inborn errors of metabolism in adults: The diagnostic odyssey of a young woman with medium‐chain acyl‐coenzyme A dehydrogenase deficiency

“…T A B L E 1 Biochemical analysis at different time of disease course of the superrefractory status epilepticus Indeed, metabolic epilepsies (epilepsies that results directly from an inherited metabolic disorder in which seizures are a core symptom of the disorder 1 ) are increasingly diagnosed, accounting for 25% of EEs of unknown etiology tested with WES. 20,21 Making a diagnosis of MCADD is crucial considering that a preventive nutritional support is necessary to achieve a good prognosis: Among patients not previously diagnosed, about 25% die during an acute episode of metabolic distress, while prognosis strongly improves after recognition of the enzyme defect. 22 Early identification of MCADD is even more important in patients with epilepsy, where diagnosis not only may reduce the burden of recurrent metabolic crises but also control seizures, prevent brain damage, and avoid development delay.…”

“…This single case report is paradigmatic of a lost generation of patients who remained undiagnosed for a long time, especially between the high number of EEs of unknown etiology. We advise adult epileptologists to consider IEMs in the diagnostic process of EEs, as early diagnosis and treatment may affect disease outcomes 20 . Indeed, metabolic epilepsies (epilepsies that results directly from an inherited metabolic disorder in which seizures are a core symptom of the disorder 1 ) are increasingly diagnosed, accounting for 25% of EEs of unknown etiology tested with WES 20,21 …”