Metabolic epilepsy: An update

Neonatal Seizures and Inborn Errors of Metabolism: An Update

“…An IEM should be suspected in a neonate presenting with seizures, particularly if unexplained and refractory [6]. Moreover, several metabolic disorders present with specific epileptic encephalopathies associated to quite suggestive EEG patterns [8]. Early Myoclonic Encephalopathy (EME) is one of the most severe, drug-resistant epilepsy with poor prognosis Abbreviations NS : neonatal seizures; CNS: central nervous system; IEM: inborn errors of metabolism; EEG: electroencephalogram; EME: early myoclonic encephalopathy; NKH: non-ketotic hyperglycinaemia; HIE: hypoxic-ischemic encephalopathy; UCDs: urea cycle disorders; CPSI: carbamyl phosphate synthetase I; OTC: ornithine transcarbamylase; ASS: arginine succinic acid synthetase; ASL: arginine succinic acid lyase: ARG: arginase; BCAA: branched chain amino acids; BCKA: branched chain ketoacids; MRI: magnetic resonance imaging; IVA: isovaleric acidemia; PPA: propionic acidemia; MMA: methylmalonic acidemia; GA1: glutaric acidemia I; PLP: pyridoxal phosphate; ALDH7A1: antiquitin gene; P6C: piperideine-6-carboxylic acid; 3-PGDH: 3-phosphoglyceric dehydrogenase; 3-PSP: 3-phosphoserine phosphatase; GAMT: guanidinacetate acid methyl transferase , OXPHOS: oxidative phosphorylation; PDHc: pyruvate dehydrogenase complex; SOD: superoxide dismutase; MOCO: molybdenum cofactor; ZS: Zellweger syndrome; NALD: neonatal adrenoleucodystrophy; RF: Refsum disease; GLD: globoid leucodystrophy.…”

“…Several IEMs may be associated to EME such as non-ketotic hyperglycinaemia (NKH), propionic or methylmalonic acidurias, methylene tetrahydrofolate reductase deficiency, GABA transaminase deficiency, serine deficiency, congenital glutamine deficiency, sulfite and xantine oxidase deficiency, and vitamin-responsive syndromes as pyridoxine, pyridoxal-phosphate, folinic and biotin deficiencies [2]. Other less specific types of seizures such as focal or generalised clonic, tonic and/or myoclonic ones may frequently occur [8].…”

“…In milder (or partial) UCD, ammonia accumulation may be triggered by illness or stress at almost any time of life, resulting in multiple mild elevations of plasma ammonia concentration; the hyperammonemia is less severe and the symptoms more subtle [6]. Seizures are frequent during the early stages of hyperammonaemia, expecially in newborns [8]. The EEG may shows variable pattern of epileptic discharge, i.e., multifocal spike-and sharp-wave discharges, repetitive paroxysmal activity, unusually low-voltage fast activity, and findings consistent with complex partial seizures [7].…”

“…Neonatal presentation with poor feeding, vomiting, lethargy and abnormal movements (rhythmic boxing and cycling movements of the limbs), fluctuating ophthalmoplegia, and seizures is quite common [8]. Early detection is critical, as initiation of therapy within the first 5 days may be associated with near normal cognitive outcome [12].…”

“…Early detection is critical, as initiation of therapy within the first 5 days may be associated with near normal cognitive outcome [12]. The diagnosis is suggested by the odor of maple syrup or burnt sugar in cerumen at 24 to 48 hours of life or in urine during the latter part of the first week and is confirmed by detecting increased values of BCAAs and BCKAs in blood and urine (2,8). MRI scan may show brain edema affecting the myelinated white matter (cerebellar white matter, dorsal brainstem, cerebral peduncles, posterior limb of the internal capsule, and peri-Rolandic cerebral white matter), thalami, and globi pallidi [5].…”