Metabolic etiologies in West syndrome

Abstract

SummaryWest syndrome (WS) is an early life epileptic encephalopathy associated with infantile spasms, interictal electroencephalography (EEG) abnormalities including high amplitude, disorganized background with multifocal epileptic spikes (hypsarrhythmia), and often neurodevelopmental impairments. Approximately 64% of the patients have structural, metabolic, genetic, or infectious etiologies and, in the rest, the etiology is unknown. Here we review the contribution of etiologies due to various metabolic disorders in the pathology of WS. These may include metabolic errors in organic molecules involved in amino acid and glucose metabolism, fatty acid oxidation, metal metabolism, pyridoxine deficiency or dependency, or acidurias in organelles such as mitochondria and lysosomes. We discuss the biochemical, clinical, and EEG features of these disorders as well as the evidence of how they may be implicated in the pathogenesis and treatment of WS. The early recognition of these etiologies in some cases may permit early interventions that may improve the course of the disease.

Treatment of infantile spasms

“…Beyond TSC, there are rare instances in which a specific metabolic etiology of IS prompts a specific therapeutic intervention, either as an alternative or adjunct to first‐line therapy . The most notable examples include pyridoxine (vitamin B6) dependency (treated with pyridoxine or leucovorin), pyridoxal‐5‐phosphate deficiency (treated with pyridoxal‐5‐phosphate), GLUT1 deficiency (treated with the ketogenic diet), and nonketotic hyperglycinemia (ameliorated to some extent by sodium benzoate and other interventions to promote central glycine clearance).…”

“…Beyond TSC, there are rare instances in which a specific metabolic etiology of IS prompts a specific therapeutic intervention, either as an alternative or adjunct to first-line therapy. 70 The most notable examples include pyridoxine (vitamin B6) dependency (treated with pyridoxine or leucovorin), pyridoxal-5-phosphate deficiency (treated with pyridoxal-5-phosphate), GLUT1 deficiency (treated with the ketogenic diet), and nonketotic hyperglycinemia (ameliorated to some extent by sodium benzoate and other interventions to promote central glycine clearance). Among these etiology-specific treatments, there is some evidence suggesting that high-dose pyridoxine is effective in the treatment of IS associated with etiologies other than pyridoxine dependency, 71,72 although other evidence suggests little or no benefit.…”

Infantile Spasms: Opportunities to Improve Care

“…causes of IS, although patients with the newly recognized "ISassociated gene" disruptions, such as ARX (Aristaless-related homeobox) and CDKL5 (cyclin-dependent kinase-like 5), and STXBP1 (syntaxin-binding protein 1), may be much more likely to develop IS. 31,35 Third/fourth tier testing could include novel gene testing or repeat brain MRI, since advances in genetic technology occur rapidly, and ongoing myelination may permit visualization of small abnormalities. Despite exhaustive evaluations, a definitive etiology is not found in 30 to 50% of children.…”

Epileptic Encephalopathies in Infants and Children

“…There are rare occasions in which a specific metabolic etiology of IS prompts a specific therapeutic intervention, either as an alternative or adjunct to first-line therapy [44]; the most notable examples include pyridoxine (vitamin B6) dependency (treated with pyridoxine or leucovorin), pyridoxal-5-phosphate deficiency (treated with pyridoxal-5-phosphate), glucose transporter type 1 (Glut1) deficiency (treated with the ketogenic diet), and nonketotic hyperglycinemia (ameliorated to some extent by sodium benzoate and other interventions to promote central glycine clearance) [45].…”