AIMS:To characterize the clinical, electrophysiological, and genetic spectrum of pediatric CMS and evaluate genotype-informed outcomes using an integrated phenotype-electrophysiology-genomics approach. METHODS:We retrospectively reviewed 36 pediatric CMS patients evaluated at a single center between 2015 and 2025. Clinical features, RNS, targeted NGS/WES variants, ventilator use, treatments, ACMG/AMP classifications, and MG-ADL outcomes were analyzed. RESULTS:Of 36 patients, 28 (77.8%) developed symptoms in the neonatal period or infancy. Biallelic variants involved 17 CMS genes; postsynaptic CMS was most common (55.6%, 20/36). COLQ and CHRNE were the most frequent genes (13.9%, 5/36 each), followed by CHAT (11.1%, 4/36). VUS were detected in 19 patients (52.8%, 19/36), including 8 with biallelic VUS supported by phenotype, neuromuscular transmission findings, treatment response, and follow-up. RNS showed a ≥ 10% decrement in 16/21 tested patients (76.2%). CHAT-CMS was associated with higher ventilator use (3/4 vs. 6/32; p = 0.041) and early mortality (3/4 vs. 1/32; p = 0.002). Median MG-ADL improved from 5 to 3 after genotype-informed therapy. CONCLUSION:Pediatric CMS shows marked genetic heterogeneity and frequent VUS-related uncertainty. Integrating phenotype, electrophysiology, and genomics supports diagnosis and mechanism-guided therapy. CHAT-CMS is high risk for early respiratory failure and mortality.

Importance:Anti-neurofascin (anti-NF) 155 antibody-positive autoimmune nodopathy is a distinct subset of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Given the increase in pediatric cases, understanding this condition is crucial. Objective:This study aimed to delineate the clinical features of children with anti-NF155 antibody-positive autoimmune nodopathy to enhance disease management strategies. Methods:We conducted a retrospective cohort study of 34 CIDP patients admitted to Beijing Children's Hospital from January 2015 to December 2024, including six with confirmed anti-NF155-antibody positivity. Their clinical symptoms, laboratory results, neuroimaging findings, and therapeutic responses were retrospectively analyzed. Results:Of the 34 patients, six (17.6%) were tested positive for anti-NF155 antibodies. The cohort was male-dominated (male-to-female ratio of 4:2) with symptoms starting primarily in school-aged children. The symptoms included progressive limb weakness, sensory ataxia, and tremors. Notably, cerebrospinal fluid (CSF) protein levels were significantly elevated in seropositive patients. Electrophysiological studies indicated sensorimotor polyneuropathy, and neuroimaging revealed nerve root thickening. While intravenous immunoglobulin (IVIG) therapy was not effective, a combination of glucocorticoids, rituximab, and plasma exchange showed promise. At the final follow-up, all patients experienced symptom relief and could perform daily activities without relapse. Interpretation:Pediatric anti-NF155 antibody autoimmune nodopathy was uncommon, featuring male dominance, and distal weakness with sensory symptoms. Additionally, the CSF protein levels were significantly elevated in seropositive patients. As IVIG treatment was ineffective, early immunosuppressive therapy was recommended. Early diagnosis and treatment are critical in reducing myelin and axonal damage.

Background Duchenne muscular dystrophy (DMD) is a disabling and life-threatening, X-linked recessive disorder caused by mutations in dystrophin. Natural history studies can inform the disease characteristics of DMD, and data from these studies can be used to plan and design clinical trials and as external controls for long-term studies. We report 12-month results from the largest natural history study of individuals with DMD in China receiving standard of care treatment.Methods This ongoing, multicentre, prospective, single-cohort study (ClinicalTrials.gov: NCT03760029) was conducted in Chinese male participants with DMD (ambulatory aged <6 years [Group 1; n = 99]; ambulatory aged >= 6 years [Group 2; n = 177], and non-ambulatory of any age [Group 3; n = 36]. The follow-up period is >24 months, with some participants followed for 30 months. The primary endpoint was time to clinical milestones due to DMD disease progression, and motor, pulmonary, and cardiac function. Secondary endpoints were quality of life (QoL) assessments.Findings Mean (standard deviation [SD]) age at screening was 3.4 (1.2), 8.6 (2.0), 12.3 (2.7) and 7.4 (3.5) years in Groups 1, 2, 3 and total respectively. Mean (SD) North Star Ambulatory Assessment (NSAA) total score at baseline was 21.2 (5.8) in Group 1, 19.5 (8.3) in Group 2 and 20.0 (7.7) in ambulatory total. Overall, the time to clinical milestones due to DMD disease progression was consistent with previous findings, in which loss of ambulation occurred at 13 years. There was a trend towards a decline over 12 months in NSAA and timed motor function from age 6 years, with the greatest reductions observed thereafter. There were no consistent trends in measures of QoL, although participants of any age generally had poorer outcomes at Month 12 versus their domain scores at baseline.Interpretation This study improves the understanding of DMD progression according to the current standards of care in the Chinese DMD population and may inform selected endpoints and patient populations in clinical trials.

Spinal muscular atrophy (SMA) is a rare, autosomal recessive, neuromuscular disease that leads to progressive muscular weakness and atrophy. Nusinersen, an antisense oligonucleotide, was approved for SMA in China in February 2019. We report interim results from a post-marketing surveillance phase 4 study, PANDA (NCT04419233), that collects data on the safety, efficacy, and pharmacokinetics of nusinersen in children with SMA in routine clinical practice in China. Participants enrolled in PANDA will be observed for 2 years following nusinersen treatment initiation. The primary endpoint is the incidence of adverse events (AEs)/serious AEs (SAEs) during the treatment period. Efficacy assessments include World Health Organization (WHO) Motor Milestones assessment, the Hammersmith Infant Neurological Examination (HINE), and ventilation support. Plasma and cerebrospinal fluid (CSF) concentrations of nusinersen are measured at each dose visit. Fifty participants were enrolled as of the January 4, 2023, data cutoff: 10 with infantile-onset (≤ 6 months) and 40 with later-onset (> 6 months) SMA. All 50 participants have received at least one dose of nusinersen; 6 have completed the study. AEs were experienced by 45 (90

Neutral lipid-storage disease with myopathy (NLSDM) is an autosomal recessive neuromuscular disorder caused by mutations in PNPLA2, and the average age at onset is 30 years. To date, only eight patients with childhood-onset NLSDM have been reported in detail. We investigated 3 unreported patients with NLSDM detected in childhood and reviewed 8 childhood-onset and 82 adult-onset patients with NLSDM documented in the literature. In the childhood-onset cohort, NLSDM presented initially as asymptomatic or paucisymptomatic hyperCKemia in 6/11 patients, and follow-up data showed onset of muscle weakness in 6/11 childhood-onset patients. In the adult-onset cohort, 95.1% (78/82) of patients showed muscle weakness. Cardiac involvement developed in 6/11 childhood-onset patients. Hepatomegaly was observed in 3/11 childhood-onset patients. Serum creatine kinase levels were elevated greater than five-fold of the upper limit of normal (ULN) in most childhood-onset patients and were elevated to less than ten-fold of the ULN in most adult-onset patients. Peripheral blood smears and muscle biopsies showed cytoplasmic lipid droplets in leukocytes and myocytes. NLSDM can present in children with asymptomatic or paucisymptomatic hyperCKemia before the onset of muscle weakness. The presence of lipid droplets in leucocytes (Jordans' anomaly) aids in diagnosing and confirming the pathogenicity of PNPLA2 variants of uncertain significance. There were no clear genotype-phenotype correlations in patients with NLSDM.

Duchenne muscular dystrophy (DMD) is a disease inherited in an X-linked recessive pattern, which is caused by the pathogenic mutation of the gene encoding Dystrophin.An increasing number of studies have confirmed the high risk of neurodevelopmental disorders in children with DMD, and that related comorbidities have distinct clinical characteristics.In this article, the research progress on neurodevelopmental disorders in children with DMD was reviewed to clarify the prevalence, clinical characteristics and high-risk factors of neurodevelopmental disorders in children with DMD.DMD therapy teams should pay attention to the evaluation, interpretation and early intervention of neurodevelopmental disorders in clinic practice, so as to improve the life quality of DMD children and help them to be-tter integrate into the society.

We initially described two children who developed Guillain-Barré syndrome (GBS) complicated by rhabdomyolysis (RML), and reviewed five adult patients from the literature. Through analysis of the clinical features, laboratory examination, treatment and prognostic data from these seven patients, we found that when GBS "meets" RML, the most prominent characteristics were the following: male dominance; limb weakness, pain and respiratory failure could be caused by multiple factors; limb weakness and respiratory muscle paralysis were more serious than with GBS alone; and the probability of mechanical ventilation was increased. Neuroelectrophysiological studies revealed axonal lesions. Close monitoring and timely identification and intervention to remedy potentially fatal complications such as electrolyte disorder multisystem complications and kidney injury are crucial. With plasma exchange, peritoneal dialysis and supportive treatment, the long-term outcome of most patients was satisfactory.

Journal Article The phenotypic spectrum of COX20-associated mitochondrial disorder Get access Rui Ban, Rui Ban Department of Neurology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, 100045, Beijing, ChinaInstitute of Neurogenomics, Computational Health Center, Helmholtz Zentrum München, Neuherberg 85764, Germany Present address: Department of Neurology, First Hospital of Tsinghua University, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert Kopajtich, Robert Kopajtich Institute of Neurogenomics, Computational Health Center, Helmholtz Zentrum München, Neuherberg 85764, GermanyInstitute of Human Genetics, School of Medicine, Technical University of Munich, Munich 81675, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Junlan Lv, Junlan Lv Department of Neurology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, 100045, Beijing, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Sarah L Stenton, Sarah L Stenton Institute of Neurogenomics, Computational Health Center, Helmholtz Zentrum München, Neuherberg 85764, GermanyInstitute of Human Genetics, School of Medicine, Technical University of Munich, Munich 81675, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Masaru Shimura, Masaru Shimura Institute of Neurogenomics, Computational Health Center, Helmholtz Zentrum München, Neuherberg 85764, GermanyDepartment of Metabolism, Chiba Children’s Hospital, 260-0842 Chiba, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Zhaoxia Wang, Zhaoxia Wang Department of Neurology, Peking University First Hospital, 100191 Beijing, China https://orcid.org/0000-0003-1742-9877 Search for other works by this author on: Oxford Academic PubMed Google Scholar Yun Yuan, Yun Yuan Department of Neurology, Peking University First Hospital, 100191 Beijing, China https://orcid.org/0000-0003-3282-9123 Search for other works by this author on: Oxford Academic PubMed Google Scholar Junling Wang, Junling Wang Department of Neurology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, 100045, Beijing, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Xiaodi Han, Xiaodi Han Department of Neurology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, 100045, Beijing, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Zhimei Liu, Zhimei Liu Department of Neurology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, 100045, Beijing, China Search for other works by this author on: Oxford Academic PubMed Google Scholar ... Show more Qiang Shi, Qiang Shi Department of Neurology, Chinese PLA General Hospital, 100853 Beijing, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Chuanqiang Pu, Chuanqiang Pu Department of Neurology, Chinese PLA General Hospital, 100853 Beijing, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Holger Prokisch, Holger Prokisch Department of Neurology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, 100045, Beijing, ChinaInstitute of Neurogenomics, Computational Health Center, Helmholtz Zentrum München, Neuherberg 85764, GermanyInstitute of Human Genetics, School of Medicine, Technical University of Munich, Munich 81675, Germany Correspondence to: Holger Prokisch Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt Institut für Neurogenomik, Ingolstädter Landstr. 1 85764 Neuherberg, Germany E-mail: prokisch@helmholtz-muenchen.de https://orcid.org/0000-0003-2379-6286 Search for other works by this author on: Oxford Academic PubMed Google Scholar Fang Fang, Fang Fang Department of Neurology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, 100045, Beijing, China Correspondence may also be addressed to: Fang Fang Department of Neurology, Beijing Children’s Hospital Capital Medical University, National Center for Children’s Health No.56 Nanlishi Road, Xicheng District, 100045 Beijing, China E-mail: fangfang@bch.com.cn Search for other works by this author on: Oxford Academic PubMed Google Scholar Matthias Elstner Matthias Elstner Department of Neurology, School of Medicine, Technical University of Munich, Munich 81675, Germany https://orcid.org/0000-0002-9119-3455 Search for other works by this author on: Oxford Academic PubMed Google Scholar Brain, Volume 145, Issue 12, December 2022, Pages e125–e127, https://doi.org/10.1093/brain/awac344 Published: 22 September 2022 Article history Received: 25 August 2022 Accepted: 28 August 2022 Published: 22 September 2022 Corrected and typeset: 09 November 2022

ObjectiveLeigh syndrome (LS) is a heterogeneous neurodegenerative disease and the most frequent pediatric manifestation of mitochondrial disease. In the largest patient collection to date, this study aimed to provide new insights into the clinical and genetic spectrum of LS, defect‐specific associations, and predictors of disease course and survival.MethodsClinical, metabolic, neuroimaging, onset, and survival data were collected from the medical records of 209 patients referred to the Beijing Children's Hospital with symmetrical basal ganglia and/or brainstem neuroimaging changes indicative of LS by 30 centers from the Chinese network of mitochondrial disease (mitoC‐NET) between January 2013 and July 2021 for exploratory analysis.ResultsPathogenic variants were identified in 52 genes, most frequently MT‐ATP6, SURF1, and PDHA1. Maternally inherited variants accounted for 42% (heteroplasmy level ≥90% in 64%). Phenotypes spanned 92 Human Phenotype Ontology terms. Elevated serum lactate (144/195), global developmental delay (142/209), and developmental regression (103/209) were most frequent. Discriminating neuroimaging and/or clinical features were identified for MT‐ATP6 (m.9176T>C), MT‐ND5, PDHA1, SUCLG1, and SURF1. Poorest survival was associated with MT‐ND5, MT‐ATP6 (m.8993T>C and m.9176T>C), SURF1, and ALDH5A1 (≤50% 3 year's survival), in contrast to milder defects with specific treatment (ECHS1 and SLC19A3, 100% 3 year's survival).InterpretationOur data define phenotype, onset, and survival of LS in a defect‐specific manner, identifying features discriminating between genetic defects and predictive of disease outcome. These findings are essential to early diagnosis, in optimizing family counseling, and to the design and monitoring of future clinical trials, the next frontier of LS research. ANN NEUROL 2022;91:466–482

Although SCN1A variants result in a wide range of phenotypes, genotype-phenotype associations are not well established. We aimed to explore the phenotypic characteristics of SCN1A associated seizure diseases and establish genotype-phenotype correlations. We retrospectively analyzed clinical data and results of genetic testing in 41 patients carrying SCN1A variants. Patients were divided into two groups based on their clinical manifestations: the Dravet Syndrome (DS) and non-DS groups. In the DS group, the age of seizure onset was significantly earlier and ranged from 3 to 11 months, with a median age of 6 months, than in the non-DS group, where it ranged from 7 months to 2 years, with a median age of 10 and a half months. In DS group, onset of seizures in 11 patients was febrile, in seven was afebrile, in two was febrile/afebrile and one patient developed fever post seizure. In the non-DS group, onset in all patients was febrile. While in the DS group, three patients had unilateral clonic seizures at onset, and the rest had generalized or secondary generalized seizures at onset, while in the non-DS group, all patients had generalized or secondary generalized seizures without unilateral clonic seizures. The duration of seizure in the DS group was significantly longer and ranged from 2 to 70 min (median, 20 min), than in the non-DS group where it ranged from 1 to 30 min (median, 5 min). Thirty-one patients harbored de novo variants, and nine patients had inherited variants. Localization of missense variants in the voltage sensor region (S4) or pore-forming region (S5–S6) was seen in seven of the 11 patients in the DS group and seven of the 17 patients in the non-DS group. The phenotypes of SCN1A-related seizure disease were diverse and spread over a continuous spectrum from mild to severe. The phenotypes demonstrate commonalities and individualistic differences and are not solely determined by variant location or type, but also due to functional changes, genetic modifiers as well as other known and unknown factors.

The founder of modern pediatric medicine in China and the first president of Beijing Children’s Hospital (BCH), academician of Chinese Academy of Sciences, Prof. Fu-Tang Chu (Prof. Futang Zhu’s name was spelled as Fu-Tang Chu since early 1930s until 1964, later on as universal use of Chinese Phonetic Alphabet for people’s name, his name has been spelled as Futang Zhu), developed a close relationship with his mentor, Prof. Charles F. McKhann, when he studied and worked in Boston Children’s Hospital, the teaching hospital of Harvard Medical School in Boston in the early 1930s. He also became a good friend of Prof. Guy M. McKhann (son of Prof. Charles F. McKhann), the founder and the first director of neurology at the Johns Hopkins Hospital (JHH) years later.

目的 描述儿童后循环动脉脑卒中的临床特点.方法 对2016年1月—2021年6月在首都医科大学附属儿童医院住院治疗的13例后循环脑梗死患儿的病历资料进行回顾性分析.结果 后循环卒中患儿发病中位年龄为7岁11个月,以男性居多(92.3％),临床症状以非特异性症状为主,其中恶心呕吐9例(69％)、头晕8例(62％)、头痛4例(31％);以共济失调体征为主.大部分患儿病因不明,其中有6例患儿完善核磁血管成像或者头颈部C T血管造影(CTA)检查均显示椎动脉管腔充盈欠佳,考虑椎动脉夹层可能.13例患儿经治疗后均有不同程度好转.结论 儿童后循环脑卒中以非特异性症状为主,容易被漏诊及延迟诊断.通过积极开展对儿童后循环脑卒中的研究,提高对该病的早期识别,及时诊治,争取最大限度减轻脑卒中带来的神经损害并降低复发率.

Aim To explore the clinical and genetic spectrum of hereditary spastic paraplegia (HSP) in Chinese children. Method This retrospective study was conducted between January 2014 and October 2021 in children clinically diagnosed with either pure HSP (pHSP) or complex HSP (cHSP). Results We investigated 45 children (32 males, 13 females; mean age [SD] at symptom onset 4 years [7 months]). clinically diagnosed with HSP and identified genetic causes in 35 patients. Most patients with autosomal dominant HSP had pHSP (16/18), whereas most patients with autosomal recessive HSP tended to have cHSP (14/16). SPG11 was the most common autosomal recessive subtype, followed by FA2H/SPG35, whereas SPAST/SPG4 was the most frequent cause of autosomal dominant HSP. Two patients with CPT1C mutations presented with a complex phenotype. Meanwhile, 10 patients were found to have likely pathogenic variants/variants of uncertain clinical significance in six genes related to HSP. Interpretation SPG11 and SPG4 were the most frequent subtypes in Chinese children with autosomal recessive HSP and autosomal dominant HSP. However, the prevalence of SPG4 was much lower than that in adults, which might be explained by the late onset of the disease. On the other hand, FA2H/SPG35 was common in our cohort, while it contributed to only a small proportion of adult cases, which might be explained by its rapid progression and early death in some patients. We also expanded the genetic and clinical spectra of SPG73.

Importance CHD2 is a member of the chromodomain helicase DNA-binding (CHD) family of proteins, which have important roles in the regulation of gene expression. Dysregulation of this protein may lead to various disorders. Objective To delineate the genotypes and phenotypes of CHD2-related epilepsy. Methods We analyzed the medical history, magnetic resonance imaging findings, and video-electroencephalogram recordings of 17 patients with CHD2 mutations in the Neurology Department of Beijing Children's Hospital from June 2016 to June 2021. Results Age at seizure onset ranged from 6 months to 10 years; the median age at onset was 4 years. Generalized tonic-clonic, myoclonic, eyelid myoclonic, atonic, atypical absence, myoclonic-atonic, and spasm seizures were observed. Ten of the 17 patients had multiple types of seizures. One patient exhibited photosensitivity epilepsy and one patient exhibited grid image-induced visual reflex epilepsy. Developmental disability was present in 14 patients, while autism features were present in five patients. Sixteen patients had de novo mutations of CHD2; one patient had an inherited variant. Eleven mutations were novel. One patient had two mutations; that patient exhibited development delay and refractory epilepsy. Seizures were controlled in eight patients, improved in seven patients, and resistant to treatment in two patients. Interpretation Phenotype severity in patients with CHD2 variants ranged from drug-responsive seizures to severe epileptic encephalopathy. Most patients exhibited developmental disorders.

Childhood-onset dystonia with optic atrophy and basal ganglia abnormalities is an extremely rare autosomal recessive mitochondrial disease caused by biallelic mutations in MECR. Using whole-exome sequencing, we identified a novel homozygous MECR mutation (c.910G > T, p.Asp304Tyr) in a Chinese patient with childhood-onset dystonia and basal ganglia abnormalities, without optic atrophy. With lipoic acid treatment, the disease progression was under control, and neither visual impairment nor optic atrophy was observed. To our knowledge, this is the first study about MECR-related mitochondrial disease in a Chinese patient and the first to report that supplementation with lipoic acid is a possible effective therapeutic strategy for this disease.

Objective: To describe the clinical features and prognosis of pediatric anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis from a single center in northern China. Methods: The clinical and laboratory characteristics of hospitalized patients with anti-NMDAR encephalitis, stratified by age, were retrospectively studied. Risk factors including relapse and long-term (followup >= 1 year) outcomes were analyzed. Results: A total of 273 patients were included between November 2011 and December 2019, and the average age of onset was 7.5 +/- 4.0 years (0.5-15.8 years). Of them, 159(58.2%) were female, and the proportion of females increased with age. Seizures were the most common initial symptom. Movement disorders(86.1%) and psychiatric(82.4%) symptoms were most frequent in the acute phase. In the acute stage, the incidence of movement disorders decreased with age (chi(2) =10.676, p = 0.011), while the proportion of psychiatric symptoms increased with age (chi(2) = 21.85, p < 0.001) The recurrence rate was 9.6% (24/250). Demyelination was an independent risk factor for relapse (p = 0.006, OR = 5.877, 95% CI: 1.658-20.835). Among the 210 patients who were followed up for more than one year, 28 patients had a poor prognosis (mRS >= 3). Onset age (p = 0.038,OR = 0.844, 95% CI: 0.720-0.991), precursor of viral encephalitis (p = 0.007,OR = 9.876, 95% CI: 1.878-51.940), and ICU admission (p = 0.023,OR = 5.924, 95% CI: 1.280-27.064) significantly affected the prognosis. The mortality rate was 2.9%. Conclusions: The characteristics of anti-NMDAR encephalitis in children are age-dependent. Early-onset, the precursor of viral encephalitis, and ICU admission may indicate poor prognosis. Demyelination may be a risk factor for recurrence. (C) 2021 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.

Objective:To summarize the clinical characteristics and genetic features of tyrosine hydroxylase deficiency(THD) caused by TH gene variants for the improvement of the understanding of the disease. Methods:The clinical and genetic data of 33 children with THD caused by TH gene variants were diagnosed in the Department of Neurology of Beijing Children′s Hospital, Capital Medical University from May 2011 to January 2020 and their data were retrospectively collected and analyzed. Results:There were 19 females and 14 males.The age at onset was ranged from 0 to 6.3 years.13 patients developed diseases, accompanied with fever after infection, and 1 patient suffered from hypoxia, 19 patients suffered from no predisposing factors.There were 7 mild TH-deficient dopa-responsive dystonia cases, 16 severe TH-deficient infantile parkinsonism with motor delay cases and 10 very severe TH-deficient progressive infantile encephalopathy cases.Clinical symptoms were fluctuating, including 26 cases of diurnal fluctuation, 22 cases of infection aggravation, and 30 cases of fatigue aggravation.The initial symptoms included tiptoeing and numbness in the limbs(7 cases), motor development retardation or degression (26 cases), fremitus (8 cases), ptosis (2 cases), and status dystonicus (3 cases). Other clinical features had hypermyotonia (23 cases), hypomyotonia (27 cases), decreased movement (27 cases), decreased facial expression (24 cases), fremitus (18 cases), tiptoeing (20 cases), talipes equinovarus (7 cases), ptosis (8 cases), oculogyric crisis (10 cases), salivation (21 cases), dysphagia (12 cases), dysarthria (16 cases), dyspnea (3 cases), increased sleep (10 cases), decreased sleep (5 cases), irritable mood (15 cases), apathetic mood (2 cases), profuse sweating (8 cases), and status dystonicus (6 cases). A total of 6 patients′ right limbs were more severe, and 14 patients′ lower limbs were more severe.Eight patients had family history, and Levodopa treatment was effective for all patients.Ten patients suffered side effects, including dyskinesia and irritability.Four patients were lost follow-up, and 29 patients were followed up between 0.8 and 13.2 years old until Ja-nuary 2020.Totally, 22 patients almost had no such symptoms.Twenty-five TH gene pathogenic variants were discovered in 33 patients.There were 13 novel variants (c.1160T>C, c.1303T>C, c.887G>A, c.1084G>A, c.1097A>T, c.734G>T, c.907C>G, c.588G>T, c.992T>G, c.755G>A, c.184-6C>T, c.1510C>T, c.910G>A) and 2 patients had c. 910G>A variant.Meanwhile, there were 5 hot variants [c.698G>A(13 cases), c.457C>T(9 cases), c.739G>A(6 cases), c.1481C>T(4 cases), c.694C>T(3 cases)]. c.910G>A(2 cases) may be the foun-der variant of Chinese population. Conclusions:THD caused by TH gene variant mostly onsets from infant, with complex clinical features.Most of these patients were severe, and only a few were very severe and mild.Very severe and mild symptoms were easily misdiagnosed.Levodopa treatment was obviously effective.A possible founder variant of Chinese population (c.910G>A) was found.c.698G>A and c. 457C>T mutations mainly appeared in patients with severe and extremely severe THD, while c. 739G>A mainly appeared in patients with mild THD.

目的 总结GCH1基因变异致儿童多巴反应性肌张力障碍(DRD)临床和遗传学特征,以提高对疾病的认识,正确诊治改变预后.方法 回顾性分析2011年5月至2020年1月首都医科大学附属北京儿童医院神经内科确诊的21例GCH1基因变异致DRD患儿的临床表现、治疗及基因突变谱,并随访.结果 女17例,男4例;起病年龄0～8岁.首次就诊时病程0.1～7.6年.起病诱因:感染后起病1例,无诱因起病20例.临床表现:经典型18例,非经典型3例;首发症状为尖足行走伴下肢僵硬18例、运动发育落后或倒退伴肢体软弱3例、眼睑下垂2例、震颤3例;部分逐渐出现躯干僵硬3例、上肢僵硬9例、肢体活动减少5例、面部表情减少3例、震颤7例、尖足行走19例、马蹄内翻足9例、眼睑下垂3例、动眼危象1例、流涎3例、吞咽困难2例、构音障碍2例、出汗多4例、睡眠增多2例、情绪淡漠1例.症状呈波动性,晨轻暮重18例,感染加重7例,疲劳加重20例.左侧肢体受累严重12例,右侧肢体受累严重3例.下肢受累严重18例,无上下肢受累优势3例.起病前运动发育落后4例,智力发育落后1例.家族史阳性3例.所有患儿均给予左旋多巴治疗后症状消失或明显缓解,2例出现异动症副反应.截止2020年1月随访,1例失访,20例随访年龄11月龄至16岁7月龄,随访时疗程0.1～8.6年,随访时16例症状基本消失,4例症状明显缓解.本组共发现21种不同的GCH1基因变异,其中10种未见文献报道的新变异(c.304A＞T, c.257C＞T, c.277A＞T, c.478A＞T, c.481C＞T, exon l duplication, exon 2+3 deletion, c.726_727insC,c.51 delG,c.151_166del).结论 GCH1基因变异致儿童DRD是一种可治疗的先天遗传代谢病,婴儿及儿童期均可起病,可早至新生儿起病,临床表现以经典型为主,误诊率高,经典型亦可出现非经典型表现,需加强早期识别.DRD患者需注意GCH1基因非编码区变异及大片段缺失重复变异的筛查.

Objective:To summarize the clinical data of patients with acute pandysautonomia (APD) and discuss the treatment and prognosis of them.Methods:A total of 13 patients with APD in the Department of Neurology, Beijing Children′s Hospital, Capital Medical University, from January 2010 to December 2019, were investigated retrospectively.The general data, clinical symptoms, autonomic nerve examination and function test, laboratory examination, treatment and follow-up were collected and analyzed.Results:There were 4 males and 9 females in 13 patients with APD, with an average age was 8 years and 5 months (3 years and 8 months to 12 years and 5 months ). The average course of disease was 94.5 d (14-410 d). The common initial symptoms were gastrointestinal motility disorder (11 cases), dysuria (3 cases), and upright syncope/vertigo (3 cases). During the course of the disease, all the patients manifested with gastrointestinal motility disfunction and dyshidrosis, glands involvement and orthostatic hypotension in 12 cases, abnormal pupil in 9 case and urinary retention in 7 case.Other symptoms included fatigue in 9 cases, emotional disorder in 4 cases, limb weakness in 2 cases, and sensory disturbance in 2 cases.All the patients were treated with intravenous immunoglobulin (IVIG), and 3 cases combined with glucocorticoid.Six patients with severe gastrointestinal symptoms were treated with intravenous nutrition; 4 patients were fed with jejunum, 3 cases of whom returned to normal diet within 1-12 months, and 1 patient was followed up for 5 years and 2 months.Hyponatremia was found in 7 cases, which recovered in 2-30 d. Nine cases were followed up for 1 month to 9 years.Seven cases were normal in daily work and study, with satisfactory nutritional status, stable mood and no relapse.Conclusions:The clinical manifestations of APD are varied.The initial symptoms are gastrointestinal motility disorders, orthostatic hypotension, urinary retention and hyponatremia.Individualized multi-disciplinary comprehensive management for symptoms, especially the comprehensive treatment of gastrointestinal motility disorders, management of postural hypotension, and the urinary system diagnosis and individualized treatment of can shorten the length of hospital stay and improve the prognosis effectively.