Case report of developmental epileptic encephalopathy caused by UBA5 gene mutation and literature review / 中华实用儿科临床杂志

ABSTRACT

Objective:To summarize the clinical and gene mutation characteristics of a child with developmental epileptic encephalopathy (DEE) caused by ubiquitin-like modifier-activating enzyme 5( UBA5 )gene mutation, and to perform literature review. Methods:Clinical characteristics and genetic test results of a case of DEE treated in Department of Neurology, Xuzhou Children′s Hospital, Xuzhou Medical University, in March 2020 were retrospectively analyzed.Relevant literatures reporting DEE cases caused by UBA5 gene mutations published before June 2020 were searched in the PubMed, CNKI, Wanfang and other online databases with the following key words epilepsy encephalopathy, developmental encephalopathy, epileptic encephalopathy, Developmental encephalopathy and UBA5. Results:A female case with 7 months and 23 days old presented epileptic spasms at 4 months of age, and the condition was uncontrolled by medication of adrenocorticotropic hormone (ACTH) and several antiepileptic drugs.The patient later progressed to recurrent, treatment-resistant seizures with arrested development, short stature, microcephaly, expressionless face, irritability, unsteady head, lack of follow-up vision, lack of laughing, and limb hypotonia.Whole exome sequencing revealed a missense mutation and a microdeletion in the UBA5 gene, and the missense mutation was paternal c. 722A>C (p.E241A), located in the 8 th exon region.The microdeletion deletion was maternally derived from the 5 th to 11 th exon, which constituted a compound heterozygous mutation.A total of 5 foreign literatures involving 18 children with DEE and 0 domestic literatures were retrieved.Combined with the present case, all 19 cases presented refractory seizures in the early infancy, and most of them were epileptic spasms (63.2%, 12/19 cases), followed by myoclonus (31.6%, 6/19 cases). The birth history of all children was unremarkable, and they later presented developmental disabilities at varying degrees, mainly including microcephaly (94.7%, 18/19 cases), lack of follow-up vision (89.5%, 17/19 cases), and short stature (94.7%, 18/19 cases), intellectual disabilities (89.5%, 17/19 cases), movement disorders (84.2%, 16/19 cases) and hypotonia (100.0%), 13/19 cases (68.4%) died.EEG results mainly revealed normal or hypsarrhythmia, but 1 case presented suppression- burst.Brain magnetic resonance imaging (MRI) findings mainly included delayed myelination (47.4%, 9/19 cases), brain atrophy (52.6%, 10/19 cases), and thin corpus callosum (26.3%, 5/19 cases). Conclusions:Children with UBA5 gene mutations often have refractory seizures in the early infancy, which are mainly epileptic spasms.They also show severe psychomotor developmental delay, microcephaly and dystonia, with an extremely poor prognosis.Brain MRI suggested varying degrees of myelin dysplasia, brain trophy, and thin corpus callosum.For cases with the above clinical manifestations, genetic testing should be considered to confirm the diagnosis.