Two siblings with acute necrotizing encephalopathy associated with variants of LARS1.

Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy of unknown etiology. The underlying mechanisms are highly heterogeneous, often including genetic backgrounds. Variants of LARS1, encoding the leucyl-tRNA synthetase 1, are responsible for infantile liver failure syndrome 1. We describe two siblings with ANE caused by compound heterozygous variants of LARS1. Patient 1 was a 17-month-old girl. She presented with generalized seizure and liver dysfunction due to influenza type A infection. Brain magnetic resonance imaging on day 4 of onset showed diffuse high-intensity signals consistent with ANE. She died on day 10. Patient 2, a younger male sibling of patient 1, had mild to moderate developmental delay and growth failure at the age of 18 months. He showed a markedly elevated level of transaminases triggered by infection with human herpesvirus 6. On day 4 of onset, he had generalized seizures. Brain computed tomography showed a diffuse symmetrical hypodensity consistent with ANE. He died on day 7. Whole exome sequencing identified the compound heterozygous variants in LARS1 (NM_020117.11) as c.83_88delinsAATGGGATA, p.(Arg28_Phe30delinsLysTryAspIle) and c.1283C>T, p.(Pro428Leu) in both siblings. The severe neurologic phenotype, found in our patients, reflects the complicated pathogenesis of LARS1-related disorder.

COVID-19 related acute necrotizing encephalopathy and acute myocarditis in an adult female: a novel case report of brain injury and myocarditis.

BACKGROUND: Acute necrotizing encephalopathy (ANE) and myocarditis are both acute, life-threatening conditions that can be triggered by COVID-19. We report a case of sequential ANE and myocarditis following a COVID-19 infection. CASE PRESENTATION: A 27-year-old female patient was brought to the emergency department due to episodes of fever for two days and a 9-h altered state of consciousness. Her condition rapidly developed into stuporous and hemodynamic instability within serval hours. Veno-arterial extracorporeal membrane oxygenation (ECMO) was rapidly initiated with other supportive treatments. The following-up MRI showed bilateral, symmetrically distributed lesions in the brainstem, bilateral hippocampal regions, and bilateral basal ganglia, consistent with ANE. The diagnosis was confirmed through the detection of SARS-CoV-2 and the exclusion of other potential causes. After weeks of medical treatment, her condition stabilized, and she was transferred for further rehabilitation treatment. CONCLUSIONS: This case study indicates that COVID-19 may simultaneously and rapidly affect the central nervous system and cardiovascular system, leading to poor outcomes. Accurate diagnosis and timely invasive bridging therapy, when necessary, can be lifesaving. Further exploration of potential mechanisms underlying COVID-19 central nervous system (CNS) and cardiovascular system manifestations will be important.

Acute necrotizing encephalopathy in adult patients with influenza: a case report and review of the literature.

The neurological complications of influenza affect mainly the pediatric Asian population. In the category of influenza-associated encephalopathy, acute necrotizing encephalopathy (ANE) is a rapidly progressive and fulminant brain disorder associated with significant neurological sequelae and mortality. To date, only a few adult cases of influenza-associated ANE have been reported. We describe a 44-year-old woman who presented with rapid progression of consciousness impairment and recurrent generalized convulsions. Influenza was diagnosed three days prior to presentation, and infection with influenza A (H3N2) pdm09 was subsequently confirmed. A diagnosis of ANE was made based on the presence of characteristic brain MRI findings, the exclusion of central nervous system infection, and an elevated serum interleukin-6 level. Pulse steroid therapy followed by tocilizumab was initiated, which led to clinical stabilization and improvement. Genetic testing revealed that the patient carried heterozygous human leukocyte antigen DQB1 03:03 and DRB1 09:01 genotypes. An analysis of the adult cases of influenza-associated ANE in the literature and the present case revealed a wide range of ages (22-71 years), a short interval (median 3 days) between the clinical onset of influenza and ANE, and a high overall mortality rate (32%). The thalamus was the most frequent (91%) location of the lesions. Our report highlights the importance of identifying this devastating but treatable neurological complication of influenza in adults, especially those of Asian descent. As a cytokine storm is the most accepted pathogenic mechanism for ANE, cytokine-directed therapies may be promising treatments for which further investigation is warranted.

Acute necrotizing encephalopathy caused by bacterial infection.

PURPOSE: Acute necrotizing encephalopathy (ANE), a rare and severe brain disorder, is typically linked to prior infections. ANE predominantly affects children, with most reported cases attributed to viral infections. However, instances of bacterial-induced ANE are infrequent. Here, we present a case of adult-onset ANE associated with bacterial infection. CASE DESCRIPTIONS: The patient exhibited a hyperinflammatory state following a urinary tract bacterial infection, with neurological function rapidly declining into a coma as the illness progressed. Gram culture of blood suggested Escherichia coli infection. A magnetic resonance imaging (MRI) scan of the brain showed symmetrical hyperintense lesions involving bilateral thalami and pons in T2-weighted and fluid-attenuated inversion recovery images. These lesions also presented with diffuse cerebral edema and diffusion restriction and subacute hemorrhage. Based on clinical symptoms and typical brain MRI, ANE was diagnosed, and the patient underwent immunotherapy. CONCLUSIONS: This case underscores the occurrence of ANE triggered by bacterial infection, expanding our understanding of the pathogens associated with this condition. It suggests that ANE may be an immune-mediated disorder rather than solely an infectious disease.

Identification of neurological complications in childhood influenza: a random forest model.

BACKGROUND: Among the neurological complications of influenza in children, the most severe is acute necrotizing encephalopathy (ANE), with a high mortality rate and neurological sequelae. ANE is characterized by rapid progression to death within 1-2 days from onset. However, the knowledge about the early diagnosis of ANE is limited, which is often misdiagnosed as simple seizures/convulsions or mild acute influenza-associated encephalopathy (IAE). OBJECTIVE: To develop and validate an early prediction model to discriminate the ANE from two common neurological complications, seizures/convulsions and mild IAE in children with influenza. METHODS: This retrospective case-control study included patients with ANE (median age 3.8 (2.3,5.4) years), seizures/convulsions alone (median age 2.6 (1.7,4.3) years), or mild IAE (median age 2.8 (1.5,6.1) years) at a tertiary pediatric medical center in China between November 2012 to January 2020. The random forest algorithm was used to screen the characteristics and construct a prediction model. RESULTS: Of the 433 patients, 278 (64.2%) had seizures/convulsions alone, 106 (24.5%) had mild IAE, and 49 (11.3%) had ANE. The discrimination performance of the model was satisfactory, with an accuracy above 0.80 from both model development (84.2%) and internal validation (88.2%). Seizures/convulsions were less likely to be wrongly classified (3.7%, 2/54), but mild IAE (22.7%, 5/22) was prone to be misdiagnosed as seizures/convulsions, and a small proportion (4.5%, 1/22) of them was prone to be misdiagnosed as ANE. Of the children with ANE, 22.2% (2/9) were misdiagnosed as mild IAE, and none were misdiagnosed as seizures/convulsions. CONCLUSION: This model can distinguish the ANE from seizures/convulsions with high accuracy and from mild IAE close to 80% accuracy, providing valuable information for the early management of children with influenza.

Biallelic variants in ribonuclease inhibitor (RNH1), an inflammasome modulator, are associated with a distinctive subtype of acute, necrotizing encephalopathy.

PURPOSE: Mendelian etiologies for acute encephalopathies in previously healthy children are poorly understood, with the exception of RAN binding protein 2 (RANBP2)-associated acute necrotizing encephalopathy subtype 1 (ANE1). We provide clinical, genetic, and neuroradiological evidence that biallelic variants in ribonuclease inhibitor (RNH1) confer susceptibility to a distinctive ANE subtype. METHODS: This study aimed to evaluate clinical data, neuroradiological studies, genomic sequencing, and protein immunoblotting results in 8 children from 4 families who experienced acute febrile encephalopathy. RESULTS: All 8 healthy children became acutely encephalopathic during a viral/febrile illness and received a variety of immune modulation treatments. Long-term outcomes varied from death to severe neurologic deficits to normal outcomes. The neuroradiological findings overlapped with ANE but had distinguishing features. All affected children had biallelic predicted damaging variants in RNH1: a subset that was studied had undetectable RNH1 protein. Incomplete penetrance of the RNH1 variants was evident in 1 family. CONCLUSION: Biallelic variants in RNH1 confer susceptibility to a subtype of ANE (ANE2) in previously healthy children. Intensive immunological treatments may alter outcomes. Genomic sequencing in children with unexplained acute febrile encephalopathy can detect underlying genetic etiologies, such as RNH1, and improve outcomes in the probands and at-risk siblings.

De novo RANBP2 variant in a fetal demise case with cerebral intraparenchymal hemorrhage.

Fetal intracranial hemorrhage (ICH) may result from a wide array of causes, either associated with maternal or fetal risk factors. In the last decade, monogenic causes of susceptibility to fetal ICH have been described, in particular in association with COL4A1 and COL4A2 genes. A peculiar form of ICH is acute necrotizing encephalitis (ANE), which is characterized by a rapid-onset severe encephalopathy following an abnormal inflammatory response to an otherwise banal infection. It usually affects healthy children and it is thought to be multifactorial, with a genetic predisposition. RANBP2 gene has been extensively associated with ANE susceptibility. We hereby present a unique case of a 42-year-old secundigravida with intrauterine fetal demise at 35 weeks of gestation. Trio-based whole-exome sequencing performed on both parents and fetal DNA showed a de novo likely pathogenic variant in the RANBP2 gene on 2q13. At the fetal autopsy, subtentorial hematoma and cerebral intraparenchymal hemorrhage were present. We speculate that this might be a new phenotypic presentation of RANBP2-associated disease. However, more similar fetal cases need to be reported in order to reinforce this hypothesis.

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OBJECTIVES: To study the clinical characteristics and prognosis of SARS-CoV-2 Omicron variant infection-associated acute necrotizing encephalopathy (ANE) in children. METHODS: A retrospective analysis was conducted on the medical data of 12 children with SARS-CoV-2 Omicron variant infection-associated ANE who were admitted to the Pediatric Intensive Care Unit, Qingdao Women and Children's Hospital from December 18 to 29, 2022. The children were divided into two groups based on outcomes: death group (7 cases) and survival group (5 cases). The clinical manifestations and auxiliary examination results were compared between the two groups. RESULTS: The median age of the 12 patients was 30 months, with a male-to-female ratio of 1:1. All patients presented with persistent high fever, with a median highest body temperature of 41℃. The median time from fever onset to seizure or consciousness disturbance was 18 hours. The death group had a higher proportion of neurogenic shock, coagulation dysfunction, as well as elevated lactate, D-dimer, interleukin-6, interleukin--8, and interleukin-10 levels compared to the survival group (P<0.05). CONCLUSIONS: Children with SARS-CoV-2 Omicron variant infection-associated with ANE commonly present with persistent high fever, rapidly progressing disease, and have a high likelihood of developing consciousness disorders and multiorgan dysfunction within a short period. The occurrence of neurogenic shock, coagulation dysfunction, and significantly elevated cytokine levels suggests an increased risk of mortality.

Clinical Experience in the Diagnosis and Treatment of Adult Acute Necrotizing Encephalopathy.

PURPOSE: We report two cases diagnosed as acute necrotizing encephalopathy (ANE) with acute onset and various clinical manifestations. METHODS: The patients' data were obtained from the medical records of the Binzhou Medical University Hospital in Binzhou, China. The clinical symptoms, laboratory examination, neuroimaging, treatment, and prognosis of the 2 patients were collected and analyzed. RESULTS: We report 2 adult ANE patients with acute onset. The first symptom was fever, followed by symptoms and signs of damage to the central nervous system. The patients were infected with herpes simplex virus and influenza virus, respectively. The main manifestation on brain magnetic resonance imaging was a mixed-signal of a "three-layer structure" in the bilateral thalamus. The first patient died. Based on the experience of the diagnosis and treatment of the first patient, combined with a review of the literature, the second patient was immediately treated with glucocorticoid pulse therapy combined with gamma globulin injection. This patient's condition was controlled, and the prognosis was good. CONCLUSIONS: This study describes the clinical symptoms, laboratory examination, neuroimaging evidence, and treatment experience of ANE in adults. We believe that the progress of the disease may be controlled, and the prognosis may be improved if glucocorticoid pulse therapy combined with gamma globulin injection is used as soon as possible.

COVID-19 related acute necrotizing encephalopathy with extremely high interleukin-6 and RANBP2 mutation in a patient with recently immunized inactivated virus vaccine and no pulmonary involvement.

BACKGROUND: We report the first case of COVID-19 associated acute necrotizing encephalopathy (ANE) without pulmonary disease in a patient with an extremely high interleukin-6 (IL-6) level and Ran Binding Protein 2 (RANBP2) mutation. CASE PRESENTATION: A 29-year-old woman recently immunized with inactivated viral vaccine-BBIBP32-CorV (Sinopharm) presented with alteration of consciousness. Her body temperature was 37° Celsius, blood pressure 42/31 mmHg, heart rate 130 bpm, respiratory rate 20 per minute, and oxygen saturation 98%. Respiratory examination was unremarkable. Neurological examination revealed stupor but preserved brainstem reflexes. Non-contrast computerized tomography of the brain showed symmetrical hypodense lesions involving bilateral thalami and cerebellar hemispheres characteristic of ANE. No pulmonary infiltration was found on chest radiograph. SARS-CoV-2 was detected by PCR; whole genome sequencing later confirmed the Delta variant. RANBP2 gene analysis revealed heterozygous Thr585Met mutation. Serum IL-6 was 7390 pg/mL. Urine examination showed pyelonephritis. Her clinical course was complicated by seizure, septic shock, acute kidney injury, and acute hepatic failure. She later developed coma and passed away in 6 days. CONCLUSIONS: ANE is caused by cytokine storm leading to necrosis and hemorrhage of the brain. IL-6 was deemed as a prognostic factor and a potential treatment target of ANE in previous studies. RANBP2 missense mutation strongly predisposes this condition by affecting mitochondrial function, viral entry, cytokine signaling, immune response, and blood-brain barrier maintenance. Also, inactivated vaccine has been reported to precipitate massive production of cytokines by antibody dependent enhancement (ADE). The true incidence of COVID-19 associated ANE is not known as were the predictors of its development. We proposed these potential two factors (RANBP2 mutation and ADE) that could participate in the pathogenesis of ANE in COVID-19 apart from SARS-CoV2 infection by itself. Further study is needed to confirm this hypothesis, specifically in the post-vaccination period. Role of RANBP2 mutation and its application in COVID-19 and ANE should be further elaborated.

A novel variation in RANBP2 associated with infection-triggered familial acute necrotizing encephalopathy.

Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy occurring in otherwise healthy children after common viral infections. The condition presents as a spectrum of symptoms ranging from infections to seizures and coma, with the potential to cause long-term neurocognitive impairment or death. Familial and recurrent ANE is referred to as ANE1. A four-generation Chinese family with ANE1 was recruited for genetic analysis. A novel missense variation, c.9041A > G, p.(Glu3014Gly) in RANBP2 was identified in this family. This study is the first to identify a novel variation in RANBP2 in a Chinese family with ANE1.

Roles of Nucleoporin RanBP2/Nup358 in Acute Necrotizing Encephalopathy Type 1 (ANE1) and Viral Infection.

Ran Binding Protein 2 (RanBP2 or Nucleoporin358) is one of the main components of the cytoplasmic filaments of the nuclear pore complex. Mutations in the RANBP2 gene are associated with acute necrotizing encephalopathy type 1 (ANE1), a rare condition where patients experience a sharp rise in cytokine production in response to viral infection and undergo hyperinflammation, seizures, coma, and a high rate of mortality. Despite this, it remains unclear howRanBP2 and its ANE1-associated mutations contribute to pathology. Mounting evidence has shown that RanBP2 interacts with distinct viruses to regulate viral infection. In addition, RanBP2 may regulate innate immune response pathways. This review summarizes recent advances in our understanding of how mutations in RANBP2 contribute to ANE1 and discusses how RanBP2 interacts with distinct viruses and affects viral infection. Recent findings indicate that RanBP2 might be an important therapeutic target, not only in the suppression of ANE1-driven cytokine storms, but also to combat hyperinflammation in response to viral infections.

Pathogenesis and Preventive Tactics of Immune-Mediated Non-Pulmonary COVID-19 in Children and Beyond.

The COVID-19 pandemic has evolved to immune escape and threatened small children and the elderly with a higher severity and fatality of non-pulmonary diseases. These life-threatening non-pulmonary COVID-19 diseases such as acute necrotizing encephalopathies (ANE) and multisystem inflammatory syndrome in children (MIS-C) are more prevalent in children. However, the mortality of multisystem inflammatory syndrome in adults (MIS-A) is much higher than that of MIS-C although the incidence of MIS-A is lower. Clarification of immunopathogenesis and genetic susceptibility of inflammatory non-pulmonary COVID-19 diseases would provide an appropriate guide for the crisis management and prevention of morbidity and fatality in the ongoing pandemic. This review article described three inflammatory non-pulmonary COVID-19 diseases including (1) meningoencephalitis (ME), (2) acute necrotizing encephalopathies (ANE), and (3) post-infectious multisystem inflammatory syndrome in children (MIS-C) and in adults (MIS-A). To prevent these life-threatening non-pulmonary COVID-19 diseases, hosts carrying susceptible genetic variants should receive prophylactic vaccines, avoid febrile respiratory tract infection, and institute immunomodulators and mitochondrial cocktails as early as possible.

Acute necrotizing encephalopathy: A case report.

Acute necrotizing encephalopathy (ANE) is a recently identified, uncommon encephalopathy affecting children. ANE is characterized by a preceding viral illness followed by seizures and rapid progressive neurologic deterioration. The diagnosis of ANE is made based on clinical presentation and characteristic multifocal brain lesions seen on computed tomography (CT). We report a previously healthy two-year-old boy who presented to our emergency department (ED) after a seizure in the setting of fever and diarrhea. He was ultimately diagnosed with ANE and treated with steroids and IVIG. Early identification of this high morbidity condition by its typical clinical picture and characteristic radiologic findings is key to allow for optimal treatment.

Familial acute necrotizing encephalopathy without RANBP2 mutation: Poor outcome.

Most childhood cases of acute necrotizing encephalopathy (ANE) involve neither family history nor recurrence. ANE occasionally occurs, however, as a familial disorder or recurs in Caucasian patients. A mutation of RAN-binding protein 2 (RANBP2) has been discovered in more than one half of familial or recurrent ANE patients. In contrast, there has been no report of this mutation in East Asia. Here, we report the first sibling cases of typical ANE in Japan, with poor outcome. DNA analysis of genes associated with ANE or other encephalopathies, including RANBP2 and carnitine palmitoyl transferase II (CPT2), indicated neither mutations nor disease-related polymorphisms. On literature review, recurrent or familial ANE without the RANBP2 mutation has a more severe outcome and greater predilection for male sex than that with the RANBP2 mutation. This suggests that there are unknown gene mutations linked to ANE.

Ferritin as an Effective Predictor of Neurological Outcomes in Children With Acute Necrotizing Encephalopathy.

BACKGROUND: Acute necrotizing encephalopathy (ANE) is a fulminant disease with poor prognosis. Cytokine storm is the important phenomenon of ANE that affects the brain and multiple organs. The study aimed to identify whether hyperferritinemia was associated with poor prognosis in patients with ANE. METHODS: All patients with ANE had multiple symmetric lesions located in the bilateral thalami and other regions such as brainstem tegmentum, cerebral white matter, and cerebellum. Neurological outcome at discharge was evaluated by pediatric neurologists using the Pediatric Cerebral Performance Category Scale. All risk factors associated with poor prognosis were further analyzed using receiver operating characteristic curve analysis. RESULTS: Twenty-nine patients with ANE were enrolled in the current study. Nine (31%) patients achieved a favorable neurological outcome, and 20 (69%) patients had poor neurological outcomes. results The group of poor neurological outcome had significantly higher proportion of shock on admission and brainstem involvement. Based on multivariate logistic regression analysis, ferritin, aspartate aminotransferase (AST), and ANE severity score (ANE-SS) were the predictors associated with outcomes. The appropriate cutoff value for predicting neurological outcomes in patients with ANE was 1823 ng/mL for ferritin, 78 U/L for AST, and 4.5 for ANE-SS. Besides, comparison analyses showed that higher level of ferritin and ANE-SS were significantly correlated with brainstem involvement (P < 0.05). CONCLUSIONS: Ferritin may potentially be a prognostic factor in patients with ANE. Hyperferritinemia is associated with poor neurological outcomes in patients with ANE and ferritin levels more than 1823 ng/mL have about eightfold increased risk of poor neurological outcome.

A Rare Case of Acute Necrotizing Encephalopathy of Childhood: A Case Report.

Acute necrotizing encephalopathy of childhood (ANEC) is a severe neurological disorder characterized by rapid-onset encephalopathy, often associated with viral infections. Acute necrotizing encephalopathy of childhood is associated with a very high mortality rate, and survivors may face long-term neurological sequelae. Acute necrotizing encephalopathy of childhood needs to be differentiated from its closest differential diagnosis, acute disseminated encephalomyelitis (ADEM). Most of the patients with ADEM recover, with a few of them having residual neurological deficits. We present a case of an eight-year-old boy with an acute history of fever, febrile seizures, and drowsiness. Magnetic resonance imaging revealed a symmetric tricolor appearance of bilateral thalamic lesions, characteristic of ANEC.

Acute necrotizing encephalopathy infected with the SARS-CoV-2 in children: Case series and literature review of clinical outcomes with the use of Tocilizumab.

BACKGROUND AND OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes acute necrotizing encephalopathy (ANE), which has a high mortality rate and severe sequelae. This study aimed to identify ANE early and evaluate the usefulness of tocilizumab in ANE treatment. METHODS: We retrospectively included eight paeefediatric ANE cases infected with SARS-CoV-2 at Xi'an Children's Hospital, China, from December 1, 2022 to May 1, 2023. A literature search was performed using the PUBMED, SPRING, SCOPUS, and EMBASE databases. This study included eleven patients. Clinical characteristics, laboratory test results, imaging features, and treatment options were analysed. RESULTS: Eight of the 19 cases (42 %) died, one (5 %) recovered, and nine (47 %) improved with residual neurological dysfunction. Eighteen patients presented with fever, with 56 % having ≥40 °C. Twelve patients (63 %) presented with dysfunction consciousness. Eight (42 %) patients experienced frequent convulsions. All eight patients in our hospital had elevated procalcitonin levels (mean: 21.32 ng/mL, range: 0.10-89.40 ng/mL). Alanine aminotransferase levels were elevated (mean: 632.81 U/L, range: 13.00-2251.00 U/L) in six patients. Seven patients showed elevated uric acid levels(mean: 396.50 µmol/L, range: 157.00-660.00 µmol/L). Brain imaging indicated that all the patients had symmetrical injuries to the bilateral thalami, accompanied by symmetrical injuries in the cerebrum, cerebellum, basal ganglia, and brain stem. Compared with the classical treatment (n = 9), the combination with tocilizumab (n = 6) showed a statistically difference in mortality (p = 0.028 < 0.05). CONCLUSION: The typical clinical manifestations of ANE in children with SARS-CoV-2 infection are acute onset with high fever, frequent convulsions and rapidly worsening disturbance of consciousness. Tocilizumab treatment could reduces mortality in ANE.

Acute Necrotizing Encephalopathy in Children: Insights and Outcomes from Iran.

Objectives: Acute necrotizing encephalopathy of childhood (ANEC) is a rare, potentially life-threatening condition. This study aimed to identify clinical profiles and outcomes of ANEC while assessing the accuracy of severity scoring in the Iranian population. Materials & Methods: The present study collected demographic, clinical, laboratory, and radiological data from children diagnosed with ANEC. Severity was measured using the ANE-Severity Score (ANE-SS), while outcomes were assessed with the Glasgow Outcome Score (GOS). This research analyzed the relationship between these scores and various parameters for statistical significance. Results: Seven patients were included over three years, with an average age of 4.4±2.7 years (5 males). ANE-SS varied from moderate to high, with most patients experiencing moderate to severe disabilities, as indicated by the GOS. Significant correlations were found with initial serum magnesium levels, pupil light reactivity, and initial GCS score (P-value < 0.05). Conclusion: Controlling initial magnesium levels may improve ANEC outcomes. Additionally, intact pupil light reactivity at admission was associated with a better prognosis.

Clinical characteristics and genetic analysis of children with Omicron BF.7.14 type novel coronavirus-related acute necrotizing encephalopathy.

Background: To explore the clinical characteristics, etiological factors, and clinical-related genetic variant of children with acute necrotizing encephalopathy (ANE) related to the Omicron BF.7.14 novel coronavirus. Methods: Genomic variations were detected through whole exome sequencing. Additionally, we summarized the clinical data to explore the inheritance patterns associated with novel coronavirus-related ANE. Results: This study included four patients (2 males and 2 females) with an average age of 2.78 ± 1.93 years. All the patients had prodromal symptoms of Omicron BF.7.14 virus infection, and exhibited symptoms such as altered consciousness, seizures and cognitive/language disturbances. Cranial MRI scans revealed damage to the thalamus, basal ganglia and brainstem. The cerebrospinal fluid (CSF) cell counts were nearly normal, but protein level in CSF increased significantly. Genetic analysis revealed a novel truncated variant of CRMP2 gene in one patient who suffered more severe coma score and prognosis and dead in the later stages. All children exhibited a decrease in the absolute count of T lymphocytes, helper T cells, suppressor T cells, and NK cells to varying degrees. Furthermore, levels of cytokines, including IL-1 ß, IL-5, IL-6 and IL-8 were significantly elevated in the CSF, especially in patient with truncated variant of CRMP2 gene. Conclusion: The Omicron BF.7.14 type novel coronavirus can lead to ANE, characterized by T cell immunosuppression and a significant increase in cytokine levels in the CSF. The truncated variation of CRMP2 gene may affect the prognosis of ANE by affecting the migration of cerebral T cells.