Abstract
Inborn errors of metabolism (IEM) are a rare cause of epilepsy, but seizures and epilepsy are frequently encountered in patients with IEM. Since these disorders are related to inherited enzyme deficiencies with resulting effects on metabolic/biochemical pathways, the term “metabolic epilepsy” can be used to include these conditions. These epilepsies can present across the life span, and share features of refractoriness to anti-epileptic drugs, and are often associated with co-morbid developmental delay/regression, intellectual, and behavioral impairments. Some of these disorders are amenable to specific treatment interventions; hence timely and appropriate diagnosis is critical to improve outcomes. In this review, we discuss those disorders in which epilepsy is a dominant feature and present an approach to the clinical recognition, diagnosis, and management of these disorders, with a greater focus on primarily treatable conditions. Finally, we propose a tiered approach that will permit a clinician to systematically investigate, identify, and treat these rare disorders.
Highlights
Inborn errors of metabolism (IEM) are the consequence of genetic defects that lead to a metabolic block in a biochemical pathway critical to cellular function, targeting many organs including the brain
Epileptic encephalopathy(EE) refers to a state where continuous and persistent epileptiform activity leads to cognitive and behavioral impairments that tend to be of a severity well beyond that expected to be caused by the underlying disease pathology alone, and is usually associated with progressive loss of cerebral function [6]
Deficiency of this enzyme has been described in a small number of infants worldwide who presented with seizures that were pyridoxine-resistant but pyridoxal phosphate (PLP)-responsive
Summary
Inborn errors of metabolism (IEM) are the consequence of genetic defects that lead to a metabolic block in a biochemical pathway critical to cellular function, targeting many organs including the brain. Epilepsies associated with IEM frequently display age-dependent clinical presentation in terms of semiology and electroclinical features [3]. This age-dependent presentation is presumably related to the sequential development of excitatory and inhibitory pathways in the neonatal brain [1]. In some IEM, accumulating compounds may cause direct neurotoxicity, and certain triggers, such as fever or intercurrent infections, may precipitate seizures and encephalopathy In these disorders, it is believed that symptoms remain latent until the accumulation of toxic products is sufficient to interfere with cell functions, as in urea cycle disorders and organic acidurias [1]. Some IEM may be associated with malformation of cortical development that may be associated with epilepsy e.g., peroxisomal disorders, pyruvate dehydrogenase deficiency, Smith–Lemli–Opitz syndrome, and congenital disorders of glycosylation
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