Early onset myoclonic encephalopathy (,EME), also known as neonatal myoclonic encephalopathy, was first described and reported by Aicardi and Goutieres in 1978. It is very rare. Clinical features Seizures usually appear in the neonatal period, 60% before 10 days of life, but also as early as a few hours after birth, with only isolated reports in the second month of life. The main seizure types are mobile myoclonus, focal seizures, giant myoclonus, and tonic spastic seizures. The seizures are brief, rapid, single or repeated in clusters, involving the face and extremities, often confined to one part of the body, such as fingers (toes), eyebrows, eyelids, corners of the mouth, a group of muscles, a limb, and can shift from one part of the body to another arbitrarily and asynchronously, with seizure frequency ranging from several times a day to tens of times a minute. The frequency of seizures varies from a few times a day to tens of times a minute, and sometimes the seizures are very slight and easily missed if not observed. Focal seizures (80% of cases) often occur after mobile myoclonus and are frequent, manifested by autonomic symptoms such as eye deviation and asphyxia, flushing, and clonic activity in different parts of the body. Massive myoclonus is a bilateral symmetrical, axial muscle twitching rapidly, which usually occurs slightly later or can begin at the beginning of the disease, often appearing between episodes of mobile myoclonus. Tonic seizures typically occur after the first month of life and manifest as widespread contractions of the trunk, usually involving the extremities. Epileptic spasms are rare and appear late, and are often considered infantile spasms when present at 3 to 4 months of age. Children with early-onset myoclonic encephalopathy tend to have psychomotor developmental arrest, uncoordinated eye movements, marked hypotonia, positive cone fasciculation signs, and sometimes a vegetative state. Etiology Metabolic and genetic etiologies are more common than structural abnormalities, with non-ketotic hyperglycinemia being more common, others such as pyridoxal-dependent or pyridoxal phosphate-dependent disorders, organic aciduria and amino acid disorders should also be considered, although the etiology remains unknown in more than 50% of patients. For EME of unknown cause, a small number of genetic studies have reported that mutations in the SLC25A22, pyridoxine-5-prime-phosphate oxidase gene (PNPO, OMIM number 603287) are strongly associated with the development of EME. The SLC25A22 gene is located on chromosome 11p15.5 and encodes a mitochondrial transporter protein (including solute carrier family 25, glutamate, mitochondrial transporter, membrane protein 22 and glutamate carrier 1), a co-transporter of mitochondrial glutamate/H+ that catalyzes the transport of glutamate with hydrogen protons. Pure missense mutations in the SLC25A22 gene were found in four children with EME, presumably due to abnormal glutamate synthesis in neurons and astrocytes, and affecting the mitochondrial whistle chain. Another boy, born in an Argentine family with a pure missense mutation, presented with severe early myoclonic epilepsy with hypotonia, microcephaly, fundus abnormalities, and an EEG showing burst suppression pattern. The PNPO gene, localized at 17q21.32, includes 7 exons and encodes pyridoxal 5-prophosphate oxidase, an enzyme that produces pyridoxal 5-prophosphate, which activates pyridoxal, an important coenzyme in neurotransmitter synthesis. Mills et al. diagnosed five preterm infants from three consanguineous families with low Apgar scores at birth, perinatal whistle suppression, unresponsive to vitamin B6 treatment, and EEG manifested as burst suppression; four died in the neonatal period. The only one survivor was treated with pyridoxine 5-prephosphate, but had acquired microcephaly, severe developmental delay, trunk hypotonia, intractable dystonia, and refractory epilepsy. Therefore, all children with EME require a comprehensive metabolic screening and genetic analysis such as SLC25A22 and PNPO can be considered in children with unknown causes. EEG The interictal EEG is characterized by a burst suppression pattern, which is more pronounced during sleep, whereas in Otawara syndrome the burst suppression pattern persists in the awake and sleep states. At 3-5 months of age, the EEG evolves into an atypical highly dysrhythmic or multifocal epileptiform discharges with slowed background activity, and the highly dysrhythmic pattern may persist for several months before eventually reverting to a burst suppression pattern. The EEG during seizures often does not correspond to wandering myoclonus, and the EEG during focal seizures or epileptiform spasms is similar to other non-syndromic cases. Key diagnostic points The onset of piecemeal, mobile myoclonus shortly after birth affects the face and extremities, mostly confined to the fingers, eyebrows and perioral area, with frequent seizures, often shifting from one site to another, and a persistent burst-inhibition pattern on the EEG. Diagnostic tests try to find the cause. Neuroimaging may be normal at the beginning of the disease, but abnormalities can be detected 3-8 months after the disease, showing widespread cortical atrophy, and some patients have progressive cortical and periventricular atrophy, or one-sided cerebral atrophy with ventricular enlargement. Given the high incidence of inborn metabolic abnormalities, genetic metabolic screening should be performed, including tests for serum amino acids (especially glycine and glycerol metabolites), organic acids, and brain crest fluid amino acids. Treatment and prognosis No effective treatment is available. The use of antiepileptic drugs, adrenocorticotropic hormones and vitamin B6 are ineffective, and the frequency of myoclonus and partial seizures may decrease with age. The long-term prognosis is poor, with approximately 50% of deaths in the first year of life and severe intellectual-motor developmental impairment in survivors.