1.Clinical and genetic characteristics of familial cases with Glucose transporter 1 deficiency syndrome.
Meijiao ZHANG ; Shimin ZHANG ; Qingping ZHANG ; Yongxin WEN ; Jiaping WANG ; Hui XIONG ; Yuwu JIANG ; Xinhua BAO
Chinese Journal of Medical Genetics 2025;42(4):424-432
OBJECTIVE:
To elucidate the clinical and genetic characteristics of familial cases with Glucose transporter type 1 deficiency syndrome (Glut1DS).
METHODS:
A survey of family history was conducted on children (proband) with Glut1DS who had visited Peking University First Hospital between November 2008 and April 2024 by focusing on the clinical manifestations of family members. Peripheral venous blood (2 mL) was collected from the pediatric patients and their parents. Genomic DNA was extracted and sequenced subsequently. Sanger sequencing was performed to validate the identified variant sites of the SLC2A1 gene in the probands and their family members. The pathogenicity of suspected variants was analyzed according to the 2015 American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants. The clinical features, auxiliary examinations, and mutational characteristics of family members with SLC2A1 variants were analyzed. This study has been approved by the Clinical Research Ethics Committee of Peking University First Hospital (Ethics No. 2021 Research 332).
RESULTS:
Among 87 cases with Glut1DS, 10 families with autosomal dominate inherited cases were identified, accounting for 11.0% of the cases. Of the 11 children, 8 were boys and 3 were girls. The onset of the disease had ranged from 3 months to 120 months (median 6 months), with 4 cases of early-onset classic type, 2 cases of late-onset classic type, and 5 cases of non-classic type. Six children had seizures, and 7 exhibited movement disorders. Seven children underwent developmental assessment, of which 3 had mild developmental delay, 2 were borderline, and 2 were normal. Nine children underwent lumbar puncture. The cerebrospinal fluid glucose levels ranged from 1.45 to 2.25 mmol/L (median 1.86 mmol/L), and the cerebrospinal fluid to blood glucose ratios ranged from 0.29 to 0.44 (median 0.35). Among the 8 fathers with SLC2A1 gene variants, 4 were asymptomatic, 2 developed paroxysmal exercise-induced movement disorders (PED) in childhood and adulthood, respectively. 1 had poor memory since childhood, 1 developed migraines during adolescence, and his sister was an asymptomatic carrier. The father with childhood-onset PED had a cerebrospinal fluid test with CSF glucose of 1.85 mmol/L. Of the 3 mothers with SLC2A1 gene mutations, 1 was an asymptomatic carrier; 2 developed PED in childhood and after the age of 20, respectively. The mother who developed PED in childhood also had psychomotor developmental delay. Genetic testing results revealed that among 10 families, 8 carried missense variants, 1 carried a nonsense variant, and 1 carried a small fragment insertion leading to a frameshift variant. Among the 11 cases, SLC2A1 gene variants in 8 children were inherited from their fathers, while in 3 cases, the variants were inherited from their mothers. The pathogenicity of the genetic variants was evaluated according to the Standards and Guidelines for the Interpretation of Sequence Variants published by the ACMG. Among the 8 variants identified in the 10 families, 4 were classified as pathogenic variants, 1 as likely pathogenic, and 3 as variants of uncertain significance (VUS). Four variant sites, including c.204_205insTCTC (p.V69fs), c.412G>C (p.G138R), c.431T>G (p.V144G), and c.875A>G (p.Y292C), were not previously reported in the literature. Among these, the latter three were categorized as VUS.
CONCLUSION
Familial Glut1DS account for 11.0% of the cases in China, with the majority of SLC2A1 gene variants inherited from the fathers, predominantly missense mutations, and with an autosomal dominant inheritance pattern. Probands tend to have earlier onset and more severe symptoms than their parents, who often present with mild or no symptoms.
Humans
;
Male
;
Female
;
Glucose Transporter Type 1/deficiency*
;
Monosaccharide Transport Proteins/deficiency*
;
Child
;
Child, Preschool
;
Carbohydrate Metabolism, Inborn Errors/genetics*
;
Mutation
;
Infant
;
Pedigree
;
Adolescent
;
Adult
2.Clinical and genetic characteristics of familial cases with Glucose transporter 1 deficiency syndrome
Meijiao ZHANG ; Shimin ZHANG ; Qingping ZHANG ; Yongxin WEN ; Jiaping WANG ; Hui XIONG ; Yuwu JIANG ; Xinhua BAO
Chinese Journal of Medical Genetics 2025;42(4):424-432
Objective:To elucidate the clinical and genetic characteristics of familial cases with Glucose transporter type 1 deficiency syndrome (Glut1DS).Methods:A survey of family history was conducted on children (proband) with Glut1DS who had visited Peking University First Hospital between November 2008 and April 2024 by focusing on the clinical manifestations of family members. Peripheral venous blood (2 mL) was collected from the pediatric patients and their parents. Genomic DNA was extracted and sequenced subsequently. Sanger sequencing was performed to validate the identified variant sites of the SLC2A1 gene in the probands and their family members. The pathogenicity of suspected variants was analyzed according to the 2015 American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants. The clinical features, auxiliary examinations, and mutational characteristics of family members with SLC2A1 variants were analyzed. This study has been approved by the Clinical Research Ethics Committee of Peking University First Hospital (Ethics No. 2021 Research 332). Results:Among 87 cases with Glut1DS, 10 families with autosomal dominate inherited cases were identified, accounting for 11.0% of the cases. Of the 11 children, 8 were boys and 3 were girls. The onset of the disease had ranged from 3 months to 120 months (median 6 months), with 4 cases of early-onset classic type, 2 cases of late-onset classic type, and 5 cases of non-classic type. Six children had seizures, and 7 exhibited movement disorders. Seven children underwent developmental assessment, of which 3 had mild developmental delay, 2 were borderline, and 2 were normal. Nine children underwent lumbar puncture. The cerebrospinal fluid glucose levels ranged from 1.45 to 2.25 mmol/L (median 1.86 mmol/L), and the cerebrospinal fluid to blood glucose ratios ranged from 0.29 to 0.44 (median 0.35). Among the 8 fathers with SLC2A1 gene variants, 4 were asymptomatic, 2 developed paroxysmal exercise-induced movement disorders (PED) in childhood and adulthood, respectively, 1 had poor memory since childhood, 1 developed migraines during adolescence, and his sister was an asymptomatic carrier. The father with childhood-onset PED had a cerebrospinal fluid test with CSF glucose of 1.85 mmol/L. Of the 3 mothers with SLC2A1 gene mutations, 1 was an asymptomatic carrier; 2 developed PED in childhood and after the age of 20 respectively. The mother who developed PED in childhood also had psychomotor developmental delay. Genetic testing results revealed that among 10 families, 8 carried missense variants, 1 carried a nonsense variant, and 1 carried a small fragment insertion leading to a frameshift variant. Among the 11 cases, SLC2A1 gene variants in 8 children were inherited from their fathers, while in 3 cases, the variants were inherited from their mothers. The pathogenicity of the genetic variants was evaluated according to the Standards and Guidelines for the Interpretation of Sequence Variants published by the ACMG. Among the 8 variants identified in the 10 families, 4 were classified as pathogenic variants, 1 as likely pathogenic, and 3 as variants of uncertain significance (VUS). Four variant sites induding, c. 204_205insTCTC (p.V69fs), c. 412G>C (p.G138R), c. 431T>G (p.V144G), and c. 875A>G (p.Y292C), were not previously reported in the literature. Among these, the latter three were categorized as VUS. Conclusion:Familial Glut1DS account for 11.0% of the cases in China, with the majority of SLC2A1 gene variants inherited from the fathers, predominantly missense mutations, and with an autosomal dominant inheritance pattern. Probands tend to have earlier onset and more severe symptoms than their parents, who often present with mild or no symptoms.
3.Analysis of teachers' willingness and influencing factors regarding the adoption of flipped classroom teaching mode in undergraduate pediatrics education
Wenrui XU ; Jianguang QI ; Ying LIAO ; Penghui WU ; Tian SANG ; Jie LIU ; Juan ZHANG ; Yuwu JIANG
Chinese Journal of Medical Education Research 2025;24(4):460-465
Objective:To investigate teachers' evaluation and willingness and the influencing factors regarding the adoption of the flipped classroom teaching mode in undergraduate pediatrics education.Methods:From December 2022 to December 2024, a questionnaire survey was conducted among the teachers who were responsible for teaching Child Health and Disease(Pediatrics) to the eight-year clinical medicine students at Peking University Health Science Center. Their views, evaluation, and willingness of implementing the flipped classroom teaching mode were investigated. Logistic regression analysis was performed using SPSS 26.0 software to explore the factors influencing teachers' willingness to adopt the flipped classroom teaching mode.Results:A total of 102 questionnaires were collected. Among the teachers, 20.59%( n=21) believed that the teaching effect of the flipped classroom was better than that of the traditional class, 58.82%( n=60) considered its effectiveness comparable, and 20.59%( n=21) found it less effective. The most influential factors affecting the effectiveness of flipped classroom were students' self-learning with online videos [(4.39±0.73) points], student participation in the flipped classrooms [(4.26±0.72) points], the adequacy of teachers' pre-class preparation [(4.18±0.65) points], and the suitability of the teaching content for the flipped classroom [(4.11±0.76) points]. Teachers believed that the flipped classroom significantly enhanced students' autonomous learning ability [(4.11±0.63) points], clinical thinking [(4.04±0.58) points], and expression skills [(3.80±0.61) points]. Additionally, 78.43%( n=80) of the teachers expressed willingness to continue participating in flipped classroom teaching. Factors influencing teachers' willingness to adopt the flipped classroom included gender, satisfaction with students' classroom participation, and personal experience with the effectiveness of the flipped classroom( P<0.05). Conclusions:The flipped classroom teaching mode is well-accepted by teachers. Students' classroom participation affects teachers' willingness to continue using the flipped classroom teaching mode. In the future, the content of flipped classroom should be arranged individually according to specific teaching objectives to increase students' classroom participation and promote the cultivation of students' ability.
4.Application and evaluation of the flipped classroom teaching method in pediatric internship for the eight-year clinical medicine program
Shiqi GUANG ; Tian SANG ; Chaomei ZENG ; Tongyan HAN ; Dan WU ; Yuwu JIANG
Chinese Journal of Medical Education Research 2025;24(4):453-459
Objective:To explore the application of the flipped classroom teaching method in pediatric internship, evaluate the feedback from both students and faculty, and provide evidence for optimizing clinical medical education strategies.Methods:Fourth-year students ( n=174) enrolled in 2019 in the eight-year clinical medicine program at Peking University Health Science Center and instructors ( n=42) participated in this study. Questionnaire survey and exit examination scores were used to assess the effectiveness of the flipped classroom method. A statistical analysis was performed using SPSS 26.0. Kruskal-Wallis test and Dunn's multiple comparisons were used to evaluate the differences in satisfaction across teaching components. Chi-square test and Fisher's exact test were applied to compare satisfaction between high-score (top 30%) and low-score (bottom 30%) student groups. Results:①Overall student satisfaction with the flipped classroom reached 91.33% ("very satisfied" + "satisfied"). High satisfaction was reported for pre-class self-learning videos (80.35%), recommended clinical guidelines (82.80%), and English literature (71.10%), while satisfaction with the flipped classroom lectures was comparatively low (52.60%), with significant differences compared to other components ( P<0.05). ②High-score students exhibited significantly lower satisfaction than low-score students across all components (overall evaluation, 84.61% vs. 98.08%, Fisher's exact test, P=0.031; pre-class videos, 53.85% vs. 76.92%, χ2=6.12, P=0.013; preparatory assignments, 61.54% vs. 80.77%, χ2=4.68, P=0.030; English literature, 53.85% vs. 75.00%, χ2=5.80, P=0.016; and flipped class lectures, 36.54% vs. 59.62%, χ2=5.55, P=0.019). ③Enhanced competency in ≥2 core areas was reported in 71.68% of students, including theoretical knowledge acquisition (49.71%), self-directed learning (35.84%), clinical thinking (31.21%), research capabilities (25.43%), and communication skills (22.54%). ④Faculty feedback indicated that 83.33% of instructors perceived the flipped classroom as equivalent or superior to traditional teaching, particularly in cultivating clinical thinking (90.48%), self-directed learning (85.71%), theoretical knowledge acquisition (76.19%), and communication skills (76.19%). ⑤Student participation willingness was primarily influenced by pre-class time investment (46.51% reported excessive effort in preparing discussion materials), while faculty engagement depended on implementation effectiveness (42.86%) and curriculum design (35.71%). Conclusions:The flipped classroom method demonstrated promising initial outcomes in pediatric internship, with high satisfaction among both students and faculty. However, further exploration and practice are required in optimizing teaching components, implementing differentiated instructional strategies, and managing time investment.
5.Long-term prognostic follow-up analysis of multiphasic myelin oligodendrocyte glycoprotein antibody-associated disease in children
Xuting CHANG ; Shangru LI ; Jie ZHANG ; Cuijie WEI ; Han XIE ; Yuan WU ; Yuehua ZHANG ; Xinhua BAO ; Yao ZHANG ; Xingzhi CHANG ; Taoyun JI ; Yuwu JIANG ; Ye WU
Chinese Journal of Pediatrics 2025;63(10):1079-1084
Objective:To investigate the long-term prognosis and related factors in children with multiphasic myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).Methods:A bidirectional cohort study was conducted. This study included 41 children with MOGAD who were treated at the Children′s Medical Center of Peking University First Hospital between January 2013 and December 2024, with a disease duration of ≥5 years. Demographic characteristics, clinical episodes, therapy, and prognostic indicators (including the expanded disability status scale (EDSS) and modified Rankin scale (mRS)) were collected. Children were stratified into relapse and non-relapse groups based on the presence or absence of relapse within 5 years of the last follow-up. χ2 test or Mann-Whitney U test was used to analyze factors associated with relapse. The Log-rank test was used to compare relapse-free rates between children with disease onset 0-<5 years and those with onset at 5-10 years. Results:A total of 41 children were enrolled, including 20 boys and 21 girls. The age at onset was 5.3 (3.8, 8.5) years, the age at last follow-up was 16.1 (13.2, 17.5) years, and the disease duration was 9.4 (8.1, 10.9) years. The annualized relapse rate (ARR) during follow-up was 0.34 (0.19, 0.56) times/year. The duration to first relapse was 0.8 (0.4, 1.5) years. At the last follow-up, the EDSS score was 0.0 (0.0, 0.0) score, and the mRS score was 0 (0, 0) score. A total of 40 children (98%) experienced relapses within the first 5 years after onset, while only 1 child (2%) relapsed at 6.7 years. The relapse rate between 5-10 years was lower than that between 0-<5 years ( HR=0.27, 95% CI 0.16-0.47, P<0.001). A total of 25 children (61.0%) exhibited clustered relapses during the disease course. There were 20 children (49%) in non-relapse groups, who were aged 16.6 (14.8, 17.6) years, disease duration 9.8 (9.3, 10.8) years at the last follow-up. Among those 20 children, 15 children (75%) had discontinued corticosteroids and immunosuppressants. The relapse group had higher clinical event rates and ARR compared to the relapse-free group (both P<0.01), the age at last follow-up was yonger ( P<0.05), while no significant differences were observed in age at onset, disease duration, or timing of immunosuppressant use (all P>0.05). Conclusions:Pediatric multiphasic MOGAD generally has a favorable prognosis, about half of patients remain relapse-free for ≥5 years at last follow-up. Relapses predominantly occur early in the disease course (mostly within 5 years of onset) and often exhibit a clustered pattern.
6.Clinical features and prognosis of febrile infection-related epilepsy syndrome in children
Jie ZHANG ; Wei LIU ; Jiong DENG ; Tian SANG ; Haipo YANG ; Qiao GUAN ; Ying ZHU ; Yuwu JIANG ; Ye WU
Journal of Chongqing Medical University 2025;50(3):280-286
Objective:To investigate the important clinical features and prognosis of febrile infection-related epilepsy syndrome(FIRES).Methods:A retrospective analysis was performed for the data of 15 children with FIRES who were hospitalized and treated in Peking University First Hospital from March 2022 to June 2024,including clinical features,treatment regimens,and prognosis,and follow-up was performed by telephone.Results:The median duration of status epilepticus was 15 days for all children.Of all 15 children,14(93.3%)were comorbid with disturbance of consciousness,8(53.3%)were comorbid with respiratory failure and underwent endotra-cheal incubation,and 13(86.7%)had been admitted to the intensive care unit.In the acute stage,7 children underwent the examination of various inflammatory factors in blood and cerebrospinal fluid,including interleukin(IL)-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,and tumor necrosis factor-α,and all 7 children had significant increases in the levels of inflammatory factors in cerebrospinal fluid,which were significantly higher than the levels of inflammatory factors in serum.Of all 15 children,12(80%)had diffuse slow wave changes on electroencephalography,and migrating focal seizures were detected in 7 children(46.7%).Cranial magnetic resonance im-aging(MRI)manifestations in the acute stage included temporal and insular cortical edema(60%),abnormal white matter signal(33.3%),and claustrum sign(13.3%),and MRI features in the chronic stage included the deepening of cerebral sulci(75%)and ventricular dilatation(33.3%).The treatment in the acute stage in-cluded intravenous drip of gamma-globulin and high-dose methyl-prednisolone in 15 children(effective in 2 children),ketogenic diet in 4 children(effective in 1 child),tocilizumab in 5 children(effective in 3 children),and anakinra in 2 children(effective in 1 child).As of the last follow-up,the median duration of disease was 14.0 months(4-65 months)for all patients,and only 2 children achieved complete seizure control,while the remaining 13 children had refractory epilepsy.Cognitive impairment was observed in 93.3%of the children.Conclusion:FIRES often has acute and severe conditions,and first-line immunotherapies often have a poor therapeutic ef-fect.Tocilizumab and anakinra may be effective in some patients with seizures in the acute stage.
7.Analysis of teachers' willingness and influencing factors regarding the adoption of flipped classroom teaching mode in undergraduate pediatrics education
Wenrui XU ; Jianguang QI ; Ying LIAO ; Penghui WU ; Tian SANG ; Jie LIU ; Juan ZHANG ; Yuwu JIANG
Chinese Journal of Medical Education Research 2025;24(4):460-465
Objective:To investigate teachers' evaluation and willingness and the influencing factors regarding the adoption of the flipped classroom teaching mode in undergraduate pediatrics education.Methods:From December 2022 to December 2024, a questionnaire survey was conducted among the teachers who were responsible for teaching Child Health and Disease(Pediatrics) to the eight-year clinical medicine students at Peking University Health Science Center. Their views, evaluation, and willingness of implementing the flipped classroom teaching mode were investigated. Logistic regression analysis was performed using SPSS 26.0 software to explore the factors influencing teachers' willingness to adopt the flipped classroom teaching mode.Results:A total of 102 questionnaires were collected. Among the teachers, 20.59%( n=21) believed that the teaching effect of the flipped classroom was better than that of the traditional class, 58.82%( n=60) considered its effectiveness comparable, and 20.59%( n=21) found it less effective. The most influential factors affecting the effectiveness of flipped classroom were students' self-learning with online videos [(4.39±0.73) points], student participation in the flipped classrooms [(4.26±0.72) points], the adequacy of teachers' pre-class preparation [(4.18±0.65) points], and the suitability of the teaching content for the flipped classroom [(4.11±0.76) points]. Teachers believed that the flipped classroom significantly enhanced students' autonomous learning ability [(4.11±0.63) points], clinical thinking [(4.04±0.58) points], and expression skills [(3.80±0.61) points]. Additionally, 78.43%( n=80) of the teachers expressed willingness to continue participating in flipped classroom teaching. Factors influencing teachers' willingness to adopt the flipped classroom included gender, satisfaction with students' classroom participation, and personal experience with the effectiveness of the flipped classroom( P<0.05). Conclusions:The flipped classroom teaching mode is well-accepted by teachers. Students' classroom participation affects teachers' willingness to continue using the flipped classroom teaching mode. In the future, the content of flipped classroom should be arranged individually according to specific teaching objectives to increase students' classroom participation and promote the cultivation of students' ability.
8.Application and evaluation of the flipped classroom teaching method in pediatric internship for the eight-year clinical medicine program
Shiqi GUANG ; Tian SANG ; Chaomei ZENG ; Tongyan HAN ; Dan WU ; Yuwu JIANG
Chinese Journal of Medical Education Research 2025;24(4):453-459
Objective:To explore the application of the flipped classroom teaching method in pediatric internship, evaluate the feedback from both students and faculty, and provide evidence for optimizing clinical medical education strategies.Methods:Fourth-year students ( n=174) enrolled in 2019 in the eight-year clinical medicine program at Peking University Health Science Center and instructors ( n=42) participated in this study. Questionnaire survey and exit examination scores were used to assess the effectiveness of the flipped classroom method. A statistical analysis was performed using SPSS 26.0. Kruskal-Wallis test and Dunn's multiple comparisons were used to evaluate the differences in satisfaction across teaching components. Chi-square test and Fisher's exact test were applied to compare satisfaction between high-score (top 30%) and low-score (bottom 30%) student groups. Results:①Overall student satisfaction with the flipped classroom reached 91.33% ("very satisfied" + "satisfied"). High satisfaction was reported for pre-class self-learning videos (80.35%), recommended clinical guidelines (82.80%), and English literature (71.10%), while satisfaction with the flipped classroom lectures was comparatively low (52.60%), with significant differences compared to other components ( P<0.05). ②High-score students exhibited significantly lower satisfaction than low-score students across all components (overall evaluation, 84.61% vs. 98.08%, Fisher's exact test, P=0.031; pre-class videos, 53.85% vs. 76.92%, χ2=6.12, P=0.013; preparatory assignments, 61.54% vs. 80.77%, χ2=4.68, P=0.030; English literature, 53.85% vs. 75.00%, χ2=5.80, P=0.016; and flipped class lectures, 36.54% vs. 59.62%, χ2=5.55, P=0.019). ③Enhanced competency in ≥2 core areas was reported in 71.68% of students, including theoretical knowledge acquisition (49.71%), self-directed learning (35.84%), clinical thinking (31.21%), research capabilities (25.43%), and communication skills (22.54%). ④Faculty feedback indicated that 83.33% of instructors perceived the flipped classroom as equivalent or superior to traditional teaching, particularly in cultivating clinical thinking (90.48%), self-directed learning (85.71%), theoretical knowledge acquisition (76.19%), and communication skills (76.19%). ⑤Student participation willingness was primarily influenced by pre-class time investment (46.51% reported excessive effort in preparing discussion materials), while faculty engagement depended on implementation effectiveness (42.86%) and curriculum design (35.71%). Conclusions:The flipped classroom method demonstrated promising initial outcomes in pediatric internship, with high satisfaction among both students and faculty. However, further exploration and practice are required in optimizing teaching components, implementing differentiated instructional strategies, and managing time investment.
9.Clinical and genetic characteristics of familial cases with Glucose transporter 1 deficiency syndrome
Meijiao ZHANG ; Shimin ZHANG ; Qingping ZHANG ; Yongxin WEN ; Jiaping WANG ; Hui XIONG ; Yuwu JIANG ; Xinhua BAO
Chinese Journal of Medical Genetics 2025;42(4):424-432
Objective:To elucidate the clinical and genetic characteristics of familial cases with Glucose transporter type 1 deficiency syndrome (Glut1DS).Methods:A survey of family history was conducted on children (proband) with Glut1DS who had visited Peking University First Hospital between November 2008 and April 2024 by focusing on the clinical manifestations of family members. Peripheral venous blood (2 mL) was collected from the pediatric patients and their parents. Genomic DNA was extracted and sequenced subsequently. Sanger sequencing was performed to validate the identified variant sites of the SLC2A1 gene in the probands and their family members. The pathogenicity of suspected variants was analyzed according to the 2015 American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants. The clinical features, auxiliary examinations, and mutational characteristics of family members with SLC2A1 variants were analyzed. This study has been approved by the Clinical Research Ethics Committee of Peking University First Hospital (Ethics No. 2021 Research 332). Results:Among 87 cases with Glut1DS, 10 families with autosomal dominate inherited cases were identified, accounting for 11.0% of the cases. Of the 11 children, 8 were boys and 3 were girls. The onset of the disease had ranged from 3 months to 120 months (median 6 months), with 4 cases of early-onset classic type, 2 cases of late-onset classic type, and 5 cases of non-classic type. Six children had seizures, and 7 exhibited movement disorders. Seven children underwent developmental assessment, of which 3 had mild developmental delay, 2 were borderline, and 2 were normal. Nine children underwent lumbar puncture. The cerebrospinal fluid glucose levels ranged from 1.45 to 2.25 mmol/L (median 1.86 mmol/L), and the cerebrospinal fluid to blood glucose ratios ranged from 0.29 to 0.44 (median 0.35). Among the 8 fathers with SLC2A1 gene variants, 4 were asymptomatic, 2 developed paroxysmal exercise-induced movement disorders (PED) in childhood and adulthood, respectively, 1 had poor memory since childhood, 1 developed migraines during adolescence, and his sister was an asymptomatic carrier. The father with childhood-onset PED had a cerebrospinal fluid test with CSF glucose of 1.85 mmol/L. Of the 3 mothers with SLC2A1 gene mutations, 1 was an asymptomatic carrier; 2 developed PED in childhood and after the age of 20 respectively. The mother who developed PED in childhood also had psychomotor developmental delay. Genetic testing results revealed that among 10 families, 8 carried missense variants, 1 carried a nonsense variant, and 1 carried a small fragment insertion leading to a frameshift variant. Among the 11 cases, SLC2A1 gene variants in 8 children were inherited from their fathers, while in 3 cases, the variants were inherited from their mothers. The pathogenicity of the genetic variants was evaluated according to the Standards and Guidelines for the Interpretation of Sequence Variants published by the ACMG. Among the 8 variants identified in the 10 families, 4 were classified as pathogenic variants, 1 as likely pathogenic, and 3 as variants of uncertain significance (VUS). Four variant sites induding, c. 204_205insTCTC (p.V69fs), c. 412G>C (p.G138R), c. 431T>G (p.V144G), and c. 875A>G (p.Y292C), were not previously reported in the literature. Among these, the latter three were categorized as VUS. Conclusion:Familial Glut1DS account for 11.0% of the cases in China, with the majority of SLC2A1 gene variants inherited from the fathers, predominantly missense mutations, and with an autosomal dominant inheritance pattern. Probands tend to have earlier onset and more severe symptoms than their parents, who often present with mild or no symptoms.
10.Long-term prognostic follow-up analysis of multiphasic myelin oligodendrocyte glycoprotein antibody-associated disease in children
Xuting CHANG ; Shangru LI ; Jie ZHANG ; Cuijie WEI ; Han XIE ; Yuan WU ; Yuehua ZHANG ; Xinhua BAO ; Yao ZHANG ; Xingzhi CHANG ; Taoyun JI ; Yuwu JIANG ; Ye WU
Chinese Journal of Pediatrics 2025;63(10):1079-1084
Objective:To investigate the long-term prognosis and related factors in children with multiphasic myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).Methods:A bidirectional cohort study was conducted. This study included 41 children with MOGAD who were treated at the Children′s Medical Center of Peking University First Hospital between January 2013 and December 2024, with a disease duration of ≥5 years. Demographic characteristics, clinical episodes, therapy, and prognostic indicators (including the expanded disability status scale (EDSS) and modified Rankin scale (mRS)) were collected. Children were stratified into relapse and non-relapse groups based on the presence or absence of relapse within 5 years of the last follow-up. χ2 test or Mann-Whitney U test was used to analyze factors associated with relapse. The Log-rank test was used to compare relapse-free rates between children with disease onset 0-<5 years and those with onset at 5-10 years. Results:A total of 41 children were enrolled, including 20 boys and 21 girls. The age at onset was 5.3 (3.8, 8.5) years, the age at last follow-up was 16.1 (13.2, 17.5) years, and the disease duration was 9.4 (8.1, 10.9) years. The annualized relapse rate (ARR) during follow-up was 0.34 (0.19, 0.56) times/year. The duration to first relapse was 0.8 (0.4, 1.5) years. At the last follow-up, the EDSS score was 0.0 (0.0, 0.0) score, and the mRS score was 0 (0, 0) score. A total of 40 children (98%) experienced relapses within the first 5 years after onset, while only 1 child (2%) relapsed at 6.7 years. The relapse rate between 5-10 years was lower than that between 0-<5 years ( HR=0.27, 95% CI 0.16-0.47, P<0.001). A total of 25 children (61.0%) exhibited clustered relapses during the disease course. There were 20 children (49%) in non-relapse groups, who were aged 16.6 (14.8, 17.6) years, disease duration 9.8 (9.3, 10.8) years at the last follow-up. Among those 20 children, 15 children (75%) had discontinued corticosteroids and immunosuppressants. The relapse group had higher clinical event rates and ARR compared to the relapse-free group (both P<0.01), the age at last follow-up was yonger ( P<0.05), while no significant differences were observed in age at onset, disease duration, or timing of immunosuppressant use (all P>0.05). Conclusions:Pediatric multiphasic MOGAD generally has a favorable prognosis, about half of patients remain relapse-free for ≥5 years at last follow-up. Relapses predominantly occur early in the disease course (mostly within 5 years of onset) and often exhibit a clustered pattern.

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