Refractive Errors, Retinal Findings, and Genotype of Tuberous Sclerosis Complex:A Retrospective Cohort Study

Purpose@#To examine the refractive errors, retinal manifestations, and genotype in tuberous sclerosis complex (TSC) patients in a Korean population. @*Materials and Methods@#A total of 98 patients with TSC were enrolled in Severance Hospital for a retrospective cohort study. The number of retinal astrocytic hamartoma and retinal achromic patch within a patient, as well as the size, bilaterality, and morphological type were studied. In addition, the refractive status of patients and the comorbidity of intellectual disability and epilepsy were also examined. @*Results@#Retinal astrocytic hamartoma was found in 37 patients, and bilateral invasion was observed in 20 patients (54%). TSC1 mutation was associated with myopia (p=0.01), while TSC2 mutation was associated with emmetropia (p=0.01). Retinal astrocytic hamartoma was categorized into three morphological types and examined as follows: type I (87%), type II (35%), and type III (14%). Single invasion of retinal astrocytic hamartoma was identified in 32% of the patients, and multiple invasions in 68%. The TSC1/ TSC2 detection rate was 91% (41/45). Among them, TSC1 variant was detected in 23 patients (54%), whereas TSC2 variant was detected in 18 patients (40%). The results showed that TSC2 mutations are correlated with a higher rate of retinal astrocytic hamartoma involvement (all p<0.05), and multiple and bilateral involvement of retinal hamartomas (all p<0.05). However, the size of retinal astrocytic hamartomas, comorbidity of epilepsy, or intellectual disability did not show correlation with the genetic variant. @*Conclusion@#TSC1 variant patients were more myopic, while TSC2 variant patients showed association with more extensive involvement of retinal astrocytic hamartoma.

Acute Necrotizing Myelitis Associated with COVID-19

Acute ascending hemorrhagic longitudinally extensive transverse myelitis is a rare inflammatory demyelinating disorder, which invades several vertebral segments and progresses rapidly and manifests severe symptoms. We present a case of acute necrotizing myelitis associated with COVID-19 infection. A 10-year-old female, with no previous medical history and no prior administration of COVID-19 vaccination, contracted COVID-19 in early April 2022. Two weeks later, she suffered from severe posterior neck pain and also presented with motor weakness and numbness in both lower extremities, making it difficult to walk independently and spontaneously void urine. Initial spinal cord MR showed longitudinally segmental extensive T2 hyperintensities. Cerebrospinal fluid (CSF) analysis revealed elevated red blood cell, normal white blood cell, and elevated protein levels and absence of oligoclonal bands. CSF culture and viral polymerase chain reaction were negative. Autoimmune work-up was negative. She was started on intravenous methylprednisolone 1g/day for 5 days and immunoglobulin (Ig) 2 g/kg for 5 days. She was also treated with six courses of therapeutic plasma exchange. Nevertheless, her pain and motor weakness persisted. She eventually developed respiratory failure. Follow-up MR presented a newly noted small hemorrhagic component. She was consequently treated with two additional courses of methylprednisolone and Ig. At 6-months follow-up, neurological examination showed improvement with normal sensory function and motor grade IV function in both upper extremities. We present the case of acute necrotizing myelitis associated with COVID-19 infection. Multiple courses of methylprednisolone and Ig showed mild improvement in motor and sensory function. However, poor prognosis was unavoidable due to rapid progression of the disease.

Social Stigma and Discrimination Toward People With Drug Addiction: A National Survey in Korea

Objective@#This study aims to understand the attitudes, stigma, and discrimination of the general adult population toward drug addiction. @*Methods@#We conducted a cross-sectional nationwide survey with 1,020 Korean adults using an Internet web-based panel. Self-reported data were collected on demographics, experience with substance abuse, perceptions of narcotic analgesic use, beliefs about the legalization of cannabis use, coping with substance abuse and addiction, and perceptions of drug risks. All statistical analysis in this study utilized the IBM SPSS Statistics 26 program. @*Results@#In this study, 1.6% of the participants reported abuse of opioid analgesics, 88.0% reported negative perceptions of drug addiction, and 76.9% reported agreeing to unfair treatment of drug addicts. Logistic regression analysis found that perceived stigma was more prevalent among women (odd ratio [OR]=2.087, p<0.01), old adults (OR=1.939, p<0.01), those with no personal experience of opioid misuse (OR=8.172, p<0.05), and those who were non-smoking (OR=2.011, p<0.01). In addition, the discriminatory attitude was more prevalent among participants with higher income (OR=1.989, p<0.001) and those who are non-smoking (OR=1.608, p<0.05). @*Conclusion@#This study provides information and guidelines for public intervention in drug addiction by identifying factors influencing social stigma and discriminatory behaviors toward drug addiction. The findings suggest that education on drug addiction prevention for the general adult population is necessary, and this education should include knowledge on coping with drug addiction and reducing stigma and discrimination toward drug addicts.

Efficacy of the Ketogenic Diet for Pediatric Epilepsy According to the Presence of Detectable Somatic mTOR Pathway Mutations in the Brain

Background@#and Purpose A multifactorial antiepileptic mechanism underlies the ketogenic diet (KD), and one of the proposed mechanisms of action is that the KD inhibits the mammalian target of rapamycin (mTOR) pathway. To test this clinically, this study aimed to determine the efficacy of the KD in patients with pathologically confirmed focal cortical dysplasia (FCD) due to genetically identifiable mTOR pathway dysregulation. @*Methods@#A cohort of patients with pathologically confirmed FCD after epilepsy surgery and who were screened for the presence of germline and somatic mutations related to the mTOR pathway in peripheral blood and resected brain tissue was constructed prospectively. A retrospective review of the efficacy of the prior KD in these patients was performed. @*Results@#Twenty-five patients with pathologically confirmed FCD and who were screened for the presence of detectable somatic mTOR pathway mutations had received a sufficient KD. Twelve of these patients (48.0%) had germline or somatic detectable mTOR pathway mutations. A response was defined as a ≥50% reduction in seizure frequency. The efficacy of the KD after 3 months of dietary therapy was superior in patients with detectable mTOR pathway mutations than in patients without detectable mTOR pathway mutations, although the difference was not statistically significant (responder rates of 58.3% vs. 38.5%, p=0.434). @*Conclusions@#A greater proportion of patients with mTOR pathway responded to the KD, but there was no statistically significant difference in efficacy of the KD between patients with and without detectable mTOR pathway mutations. Further study is warranted due to the smallness of the sample and the limited number of mTOR pathway genes tested in this study.

Effects of Cannabidiol on Adaptive Behavior and Quality of Life in Pediatric Patients With Treatment-Resistant Epilepsy

Background@#and Purpose Data regarding the effects of cannabidiol (CBD) on the quality of life (QOL) are currently inadequate. We assessed the QOL of pediatric patients with epilepsy who were treated with CBD. @*Methods@#This prospective, open-label study included pediatric and adolescent patients (aged 2–18 years) with Dravet syndrome or Lennox-Gastaut syndrome. Oral CBD was administered at 10 mg/kg/day. The Korean version of the Quality Of Life in Childhood Epilepsy (QOLCE) questionnaire was administered when CBD treatment began and again after 6 months. Adaptive behavior was measured using the Korean versions of the Child Behavior Checklist (K-CBCL) and the second edition of the Vineland Adaptive Behavior Scales (Vineland-II). @*Results@#This study included 41 patients (11 with Dravet syndrome and 30 with LennoxGastaut syndrome), of which 25 were male. The median age was 4.1 years. After 6 months, 26.8% (11/41) of patients experienced a ≥50% reduction in the number of seizures. The total score for the QOLCE questionnaire did not change from baseline to after 6 months of CBD treatment (85.71±39.65 vs. 83.12±48.01, respectively; p=0.630). The score in the motor skills domain of Vineland-II reduced from 48.67±13.43 at baseline to 45.18±14.08 after 6 months of treatment (p=0.005). No other Vineland-II scores and no K-CBCL scores had changed after 6 months of CBD treatment. @*Conclusions@#CBD is an efficacious antiseizure drug used to treat Dravet syndrome and Lennox-Gastaut syndrome. However, it did not improve the patient QOL in our study, possibly because all of our patients had profound intellectual disabilities.

Treatment strategies targeting specific genetic etiologies in epilepsy

Recent genetic advances allow for identification of the genetic etiologies of epilepsy within individual patients earlier and more frequently than ever. Specific targeted treatments have emerged from improvements in understanding of the underlying epileptogenic pathophysiology. These targeted treatment strategies include modifications of ion channels or other cellular receptors and their function, mechanistic target of rapamycin signaling pathways, and substitutive therapies in hereditary metabolic epilepsies. In this review, we explore targeted treatments based on underlying pathophysiologic mechanisms in specific genetic epilepsies.

Clinical Features and Treatment Outcomes of Seronegative Pediatric Autoimmune Encephalitis

Background@#and Purpose New diagnostic criteria for pediatric autoimmune encephalitis (AIE) have been introduced recently. A substantial proportion of cases of pediatric AIE are diagnosed as seronegative based on these criteria, and so the clinical characteristics of this group remain to be investigated. @*Methods@#This study included 46 pediatric patients younger than 18 years with suspected AIE. Clinical features, laboratory or radiological findings, and treatment outcomes were compared between seronegative and seropositive patients. @*Results@#Nine (19.6%) of the 46 patients were diagnosed as seropositive AIE. All of the patients with seropositive AIE had anti-N-methyl-D-aspartate receptor antibodies. Commonly identified neuropsychiatric symptoms were altered mental status, cognitive dysfunction, seizure, speech dysfunction, and psychotic disorder in both the seronegative and seropositive groups. Immunotherapy produced favorable treatment outcomes in both the seropositive (n=7, 77.8%) and seronegative (n=35, 94.6%) AIE patients. Treatment outcomes for first-line immunotherapy were better in seronegative AIE than seropositive AIE patients (p=0.003), and hence a smaller proportion of seronegative patients required second-line treatment (p=0.015). @*Conclusions@#Pediatric seronegative AIE patients showed clinical presentations similar to those of seropositive AIE patients, with favorable treatment outcomes after immunotherapy.

Treatment strategies targeting specific genetic etiologies in epilepsy

Recent genetic advances allow for identification of the genetic etiologies of epilepsy within individual patients earlier and more frequently than ever. Specific targeted treatments have emerged from improvements in understanding of the underlying epileptogenic pathophysiology. These targeted treatment strategies include modifications of ion channels or other cellular receptors and their function, mechanistic target of rapamycin signaling pathways, and substitutive therapies in hereditary metabolic epilepsies. In this review, we explore targeted treatments based on underlying pathophysiologic mechanisms in specific genetic epilepsies.

Clinical Features and Treatment Outcomes of Seronegative Pediatric Autoimmune Encephalitis

Background@#and Purpose New diagnostic criteria for pediatric autoimmune encephalitis (AIE) have been introduced recently. A substantial proportion of cases of pediatric AIE are diagnosed as seronegative based on these criteria, and so the clinical characteristics of this group remain to be investigated. @*Methods@#This study included 46 pediatric patients younger than 18 years with suspected AIE. Clinical features, laboratory or radiological findings, and treatment outcomes were compared between seronegative and seropositive patients. @*Results@#Nine (19.6%) of the 46 patients were diagnosed as seropositive AIE. All of the patients with seropositive AIE had anti-N-methyl-D-aspartate receptor antibodies. Commonly identified neuropsychiatric symptoms were altered mental status, cognitive dysfunction, seizure, speech dysfunction, and psychotic disorder in both the seronegative and seropositive groups. Immunotherapy produced favorable treatment outcomes in both the seropositive (n=7, 77.8%) and seronegative (n=35, 94.6%) AIE patients. Treatment outcomes for first-line immunotherapy were better in seronegative AIE than seropositive AIE patients (p=0.003), and hence a smaller proportion of seronegative patients required second-line treatment (p=0.015). @*Conclusions@#Pediatric seronegative AIE patients showed clinical presentations similar to those of seropositive AIE patients, with favorable treatment outcomes after immunotherapy.

Cannabidiol for Treating LennoxGastaut Syndrome and Dravet Syndrome in Korea

Background@#For the first time in Korea, we aimed to study the efficacy and safety of cannabidiol (CBD), which is emerging as a new alternative in treating epileptic encephalopathies. @*Methods@#This study was conducted retrospectively with patients between the ages of 2–18 years diagnosed with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) were enrolled from March to October 2019, who visited outpatient unit at 3 and 6 months to evaluate medication efficacy and safety based on caregiver reporting. Additional evaluations, such as electroencephalogram and blood tests, were conducted at each period also. CBD was administered orally at a starting dose of 5 mg/kg/day, and was maintained at 10 mg/kg/day. @*Results@#We analyzed 34 patients in the LGS group and 10 patients in the DS group between the ages of 1.2–15.8 years. In the 3-month evaluation, the overall reduction of seizure frequency in the LGS group was 52.9% (>50% reduction in 32.3% of the cases), and 29.4% in the 6-month evaluation (more than 50% reduction in 20.6%). In DS group, the reduction of seizure frequency by more than 50% was 30% and 20% in the 3-month and 6-month evaluation, respectively. Good outcomes were defined as the reduction of seizure frequency by more than 50% and similar results were observed in both LGS and DS groups. Adverse events were reported in 36.3% of total patients of which most common adverse events were gastrointestinal problems. However, no life-threatening adverse event was reported in both LGS and DS during the observation period. @*Conclusion@#In this first Korean study, CBD was safe and tolerable for use and could be expected to potentially reduce the seizure frequency in pediatric patients with LGS or DS.

Cannabidiol for Treating LennoxGastaut Syndrome and Dravet Syndrome in Korea

Background@#For the first time in Korea, we aimed to study the efficacy and safety of cannabidiol (CBD), which is emerging as a new alternative in treating epileptic encephalopathies. @*Methods@#This study was conducted retrospectively with patients between the ages of 2–18 years diagnosed with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) were enrolled from March to October 2019, who visited outpatient unit at 3 and 6 months to evaluate medication efficacy and safety based on caregiver reporting. Additional evaluations, such as electroencephalogram and blood tests, were conducted at each period also. CBD was administered orally at a starting dose of 5 mg/kg/day, and was maintained at 10 mg/kg/day. @*Results@#We analyzed 34 patients in the LGS group and 10 patients in the DS group between the ages of 1.2–15.8 years. In the 3-month evaluation, the overall reduction of seizure frequency in the LGS group was 52.9% (>50% reduction in 32.3% of the cases), and 29.4% in the 6-month evaluation (more than 50% reduction in 20.6%). In DS group, the reduction of seizure frequency by more than 50% was 30% and 20% in the 3-month and 6-month evaluation, respectively. Good outcomes were defined as the reduction of seizure frequency by more than 50% and similar results were observed in both LGS and DS groups. Adverse events were reported in 36.3% of total patients of which most common adverse events were gastrointestinal problems. However, no life-threatening adverse event was reported in both LGS and DS during the observation period. @*Conclusion@#In this first Korean study, CBD was safe and tolerable for use and could be expected to potentially reduce the seizure frequency in pediatric patients with LGS or DS.

Prognostic Factors for Absence Epilepsy in Childhood / 대한소아신경학회지

PURPOSE@#Childhood absence epilepsy (CAE) is a common form of idiopathic generalized epilepsy with onset middle childhood and has typically a good prognosis, but remission rates vary. We aimed to analyze unfavorable prognostic factors in children initially diagnosed with CAE.@*METHODS@#We retrospectively reviewed 48 patients under 13 years of age who were diagnosed with CAE at the Severance Children's Hospital, Seoul, Korea. We analyzed clinical information including comorbidity through neuropsychological test.@*RESULTS@#Thirteen of the 48 patients (27%) showed an unfavorable prognosis, with clinical seizures or seizure waves on electroencephalogram persistent even after 12 months of anticonvulsant therapy. The mean age at absence seizure onset was 6.51±2.36 years. The most commonly used antiepileptic drug (AED) was ethosuximide, and the median duration of initial AEDs was 25.63±24.41 months. The presence of comorbidity and clinical absence seizures after 6 months of AEDs correlated with an unfavorable prognosis. Motor seizures were the most unfavorable prognostic factor during follow-up.@*CONCLUSION@#This study shows that clinical absence seizures after 6 months of AED, comorbidity, and motor seizure are the most important predictive factors of an unfavorable prognosis for absence epilepsy in childhood. This study suggests that when these factors are observed, early intervention needs to be considered.

Clinical Features and Treatment Efficacy in CDKL5 Mutation-Related Epileptic Encephalopathy in the Infant / 대한소아신경학회지

PURPOSE@#Mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene are associated with epileptic encephalopathy and severe cognitive impairment. We aim to characterize the association between this gene and treatment efficacy.@*METHODS@#We retrospectively analyzed 10 patients who were treated at Severance Children's Hospital for epileptic encephalopathy who were subsequently diagnosed with a CDKL5 mutation using next-generation sequencing.@*RESULTS@#Electroencephalography (EEG) results showed generalized pattern abnormalities in 60% (6/10) of patients with CDKL5 mutations. We analyzed the effects of three treatments, namely antiepileptic drugs (AEDs), ketogenic diet (KD), and steroids. A more than 50% reduction in seizures was observed in 12% (1/8) of patients treated with clobazam. KD treatment proved ineffective in most cases. In addition, a more than 50% reduction in seizures was observed in 57% (4/7) of patients treated with steroids. EEG analysis of patients treated effectively with steroids revealed that 75% (3/4) showed hypsarrhythmia and 25% (1/4) showed focal epileptiform.@*CONCLUSION@#In this study, as in other studies, AEDs and KD did not effectively control seizures in most patients with a CDKL5 mutation. However, steroid therapy reduced the frequency of seizures in patients who also exhibited hypsarrhythmia. This suggests that steroid treatment is helpful in cases of hypsarrhythmia with CDKL5 mutations.

Treatment Response to Acquired Aphasia with Seizures and Prognosis through Electroencephalogram on Cognitive Function / 대한소아신경학회지

PURPOSE@#Acquired epileptic aphasia (AEA) accompanied by electroencephalogram (EEG) abnormality is a rare disease; therefore, there are few studies investigating the prognostic factors and treatment efficacy. We aimed to determine the therapeutic effects and prognostic factors for clinical seizure and neuropsychological function in acquired aphasia patients.@*METHODS@#We retrospectively studied cases of AEA diagnosed at Severance Children's Hospital from January 2013 to October 2017. We evaluated the efficacy of antiepileptic drugs, steroids, and ketogenic diets (KD) in treating acquired aphasia. The EEG patterns and prognostic factors were predicted by the background EEG and frequency of spike and wave during sleep (SWS).@*RESULTS@#The study analyzed 20 patients, 11 male and 9 female, with AEA. Aphasia most commonly occurred at 4 years of age, and clinical seizure was most likely to occur between 2 and 4 years of age and focal seizures were the most common seizure type. KD was shown to be the best treatment for clinical seizure in AEA patients. Patients with normal EEG background showed better responses to clinical seizure treatment and improvements in neuropsychological function.@*CONCLUSION@#KD and steroids generate the best therapeutic effects for clinical seizure in AEA patients. Improvements in neuropsychological function in AEA patients may be related to the EEG background and the SWS patterns. Additionally, the results suggest that the response of clinical seizure to antiepileptic drugs may also be related to the EEG background. However, the current study had some limitations and further research is needed.

Adverse Events During Perampanel Adjunctive Therapy in Intractable Epilepsy

BACKGROUND AND PURPOSE: Perampanel is the first α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-receptor antagonist developed to treat epilepsy. The effects of either rapid or slow dose titration on adverse events remain to be elucidated. METHODS: Eighty-five patients received perampanel between March 2016 and August 2016. Patients were divided into two groups according to their dosing schedule: rapid dose titration (2-mg increments at intervals of 1 to 2 weeks) and slow dose titration (2-mg increments at intervals of at least 3 weeks). Seizure frequency and adverse events were analyzed over 3 months. RESULTS: Adverse events were reported by 47 (58%) of the 81 patients analyzed, with 12 (15%) patients discontinuing perampanel due to adverse events. Common adverse events included dizziness (n=30, 37%), aggressive mood and behavior (n=19, 24%), gait disturbance (n=16, 20%), and sleep problems (n=10, 12.4%). The overall adverse events were similar in the slow-titration group (38 of 61 patients) and the rapid-titration group (8 of 20 patients, p=0.081). However, none of the 20 patients in the slow-titration group experienced gait disturbance, compared with 16 of the 61 patients in the rapid-titration group (p=0.009), while appetite change was experienced by 4 patients in the slow-titration group but only 1 in the rapid-titration group (p=0.003). No relationship was noted between adverse events and the maximum dose of perampanel (p=0.116). Sex differences were observed, with the response to perampanel being better and the rate of adverse events being higher in females (p=0.015 and p=0.046, respectively). CONCLUSIONS: Slow titration of perampanel may reduce perampanel-related adverse events.

Alice in Wonderland Syndrome in a Child with an Electroencephalographic Abnormality: A Case Report / 대한소아신경학회지

Alice in wonderland syndrome (AWS) is a paroxysmal disorder with distorted body image, including altered perceptions of size, mass, or shape. In fact, altered body image is the classic symptom of AWS. However, young children and adolescents younger than 15 years with AWS usually show visual symptoms, including micropsia or teleopsia. The most common visual symptom with AWS is micropsia. There are several theories of the etiology of AWS, the most popular of which is migraine. The second most frequently mentioned etiologic theory of AWS is that it is infection-induced. Finally, abnormal brain electrical activity, such as epilepsy, is another possible cause of AWS. We herein report a case of 9-year-old boy who was admitted with visual disturbances characterized by microteleopsia and pelopsia. He denied headache, but his mother had a history of migraine. His general physical examination was unremarkable. Brain magnetic resonance imaging did not show any abnormal findings, but an electroencephalogram showed abnormal discharges. The patient was prescribed an antiepileptic drug, which improved his symptoms.

Age-Based Characteristics of West Syndrome in Patients with Mitochondrial Disease / 대한소아신경학회지

PURPOSE: West syndrome is a severe form of age-specific epilepsy that typically affects infants younger than 2 years of age with mitochondrial disease. We aimed to examine age-specific characteristics of the syndrome in these patients. METHODS: We retrospectively analyzed 54 patients with West syndrome diagnosed with mitochondrial disease between March 2006 and March 2016. We compared treatment strategies and diagnostic and clinical variables between patients with early-onset ( < 6 months of age) and late-onset (≥6 months of age) seizures. RESULTS: Seizure was the first symptom in 30 (90.9%) and 13 (65%) patients of the early-onset and late-onset groups, respectively (P=0.046). Delayed development was observed in 3 (9.1%) and 7 (35%) patients of the early-onset and late-onset groups, respectively (P=0.023). Lactate levels were normal in 17 patients (55%) of the early-onset group and 5 (25%) of the late-onset group (P=0.036), while initial brain magnetic resonance imaging (MRI) findings were normal in 23 (67.6%) and 8 (40%) patients of the early-onset and late-onset groups, respectively. Final MRI findings were abnormal in 32 patients (94.1%) of the early-onset group and 18 (90%) of the late-onset group (P=0.036). Although ketogenic diets reduced seizure frequency in both groups, the difference was not significant. CONCLUSION: There is no significant difference in epilepsy-related variables when patients are divided based on a cut-off age of 6 months. However, differences in the first symptom at onset and MRI findings were observed. Although lactate levels were not of significant diagnostic value in the early-onset group, they may be in the late-onset group.

Early Diagnosis of KBG Syndrome Using Diagnostic Exome Sequencing / 대한소아신경학회지

KBG syndrome is a rare neurodevelopmental disorder characterized by intellectual disability, skeletal anomalies, short stature, craniofacial dysmorphism, and macrodontia. ANKRD11 gene mutation and 16q24.3 microdeletion have been reported to cause KBG syndrome. Here, we report two patients with ANKRD11 mutations who initially presented with neurologic symptoms such as developmental delay and seizures. Patient 1 was a 23-month-old boy who presented with a global developmental delay. Language delay was the most dominant feature. He had hypertelorism, hearing impairment, and behavior problems characterized as hyperactivity. A c.1903_1907delAAACA (p.Lys635GInfsTer26) mutation in ANKRD11 was identified with diagnostic exome sequencing. Patient 2 was a 14-month-old boy with developmental delay and seizure. He also had atrial septum defect, and ventricular septal defect. Generalized tonic seizures began at the age of 8 months. Electroencephalography showed generalized sharp and slow wave pattern. Seizures did not respond to antiepileptic drugs. A loss of function mutation c.5350_5351delTC (p.ser1784HisfsTer12) in ANKRD11 was identified with diagnostic exome sequencing. In both cases, characteristic features of KBG syndrome such as short stature or macrodontia, were absent, and they visited the hospital due to neurological symptoms. These findings suggest that more patients with mild phenotypes of KBG syndrome are being recognized with advances in diagnostic exome sequencing genetic technologies.

Alpers-Huttenlocher Syndrome First Presented with Hepatic Failure: Can Liver Transplantation Be Considered as Treatment Option? / 대한소아소화기영양학회지

Mitochondria play essential role in eukaryotic cells including in the oxidative phosphorylation and generation of adenosine triphosphate via the electron-transport chain. Therefore, defects in mitochondrial DNA (mtDNA) can result in mitochondrial dysfunction which leads to various mitochondrial disorders that may present with various neurologic and non-neurologic manifestations. Mutations in the nuclear gene polymerase gamma (POLG) are associated with mtDNA depletions, and Alpers-Huttenlocher syndrome is one of the most severe manifestations of POLG mutation characterized by the clinical triad of intractable seizures, psychomotor regression, and liver failure. The hepatic manifestation usually occurs late in the disease's course, but in some references, hepatitis was reportedly the first manifestation. Liver transplantation was considered contraindicated in Alpers-Huttenlocher syndrome due to its poor prognosis. We acknowledged a patient with the first manifestation of the disease being hepatic failure who eventually underwent liver transplantation, and whose neurological outcome improved after cocktail therapy.

Alpers-Huttenlocher Syndrome First Presented with Hepatic Failure: Can Liver Transplantation Be Considered as Treatment Option? / 대한소아소화기영양학회지

Mitochondria play essential role in eukaryotic cells including in the oxidative phosphorylation and generation of adenosine triphosphate via the electron-transport chain. Therefore, defects in mitochondrial DNA (mtDNA) can result in mitochondrial dysfunction which leads to various mitochondrial disorders that may present with various neurologic and non-neurologic manifestations. Mutations in the nuclear gene polymerase gamma (POLG) are associated with mtDNA depletions, and Alpers-Huttenlocher syndrome is one of the most severe manifestations of POLG mutation characterized by the clinical triad of intractable seizures, psychomotor regression, and liver failure. The hepatic manifestation usually occurs late in the disease's course, but in some references, hepatitis was reportedly the first manifestation. Liver transplantation was considered contraindicated in Alpers-Huttenlocher syndrome due to its poor prognosis. We acknowledged a patient with the first manifestation of the disease being hepatic failure who eventually underwent liver transplantation, and whose neurological outcome improved after cocktail therapy.