Objective Hereditary Neuropathy with Liability to Pressure Palsy (HNPP) in childhood presents with diverse clinical manifestations. Early recognition and accurate diagnosis are critical for prognostic assessment and for providing appropriate guidance on life management. Methods We conducted a retrospective single-center cohort study of 14 pediatric HNPP patients admitted to Beijing Children’s Hospital from January 2018 to June 2026. Clinical presentations and electrophysiological findings were analyzed retrospectively. Results Among the 14 patients, 6 cases were male and 8 cases were female. The age at onset ranged from 6 to 12 years, with 71.4% presenting within the first decades of life. The majority presented with unilateral lower extremity weakness and numbness, most commonly peroneal nerve palsy. Nerve conduction studies revealed sensori-motor demyelinating polyneuropathy, with conduction abnormalities in some patients. Moreover, early neurophysiological examinations may reveal abnormalities that were not specific to uniform demyelinating polyneuropathy. Conclusion The clinical spectrum of HNPP in childhood is heterogeneous, and electrophysiological findings are valuable in supporting the diagnosis. Genetic testing should be considered when HNPP is clinically suspected, even if nerve conduction study findings are atypical. Early diagnosis is essential to reduce unnecessary examinations and to facilitate timely prevention education.

Since meningoencephalitis with prominent meningeal involvement was first described as a rare phenotype of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), sporadic cases have been reported. However, most of the reports were case reports and small sample cohorts. We conducted a retrospective analysis of paediatric patients with MOG antibody-associated meningoencephalitis without cerebral parenchyma involvement on imaging at Beijing Children’s Hospital between 2017 and 2024. Upon reviewing the records of 320 MOG antibody-positive paediatric patients in our centre, we identified 18 (6

Diffuse alveolar hemorrhage (DAH) is a group of rare but life-threatening conditions characterized by bleeding into the alveolar spaces, often associated with various etiologies. Epithelioid sarcoma (ES) is a rare and aggressive soft tissue sarcoma that has never been reported to be associated with DAH. We report a rare case of ES in a pediatric patient presenting with DAH and intracranial hemorrhagic lesions. Diagnostic evaluations included high-resolution chest CT (HRCT), bronchoscopy, brain MRI, lung biopsy, Positron emission tomography - computed tomography (PET-CT), and biopsy of a mass in the right thigh. Fluorescence in situ hybridization was performed to detect SMARCB1 (INI1) gene deletion. A 13-year-old male presented with anemia and later developed hemoptysis with a decreased hemoglobin level. HRCT revealed bilateral ground-glass opacities consistent with DAH. Extensive autoimmune and infectious workups were all negative. Brain MRI demonstrated microhemorrhages. Despite corticosteroid therapy, the patient’s condition worsened. PET-CT identified a hypermetabolic soft tissue mass in the right thigh, which on histopathological examination was confirmed as INI1-deficient ES. FISH analysis confirmed INI1 deletion. This case highlights the diagnostic challenges of INI1-deficient ES presenting with DAH and underscores the importance of considering malignancy in pediatric patients with atypical DAH. Multidisciplinary approaches, including advanced imaging and molecular diagnostics, are crucial for accurate diagnosis and management.

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.

目的 探讨不同年龄段儿童动脉缺血性脑卒中(AIS)的病因.方法 回顾性分析首都医科大学附属北京儿童医院神经内科病房2016年1月至2020年12月收治的AIS患儿资料,根据2019年美国心脏协会和美国卒中协会儿童脑卒中的管理指南将AIS病因分为心源性、易栓症、脑动脉病、其他、病因不详5大类.根据年龄分为婴幼儿(＞28d至＜3岁)、学龄(前)儿童(3～＜10岁)和青少年(10～＜18岁).分析不同病因患儿的临床特点.结果 共纳入129例AIS患儿.脑动脉病是首要病因,共47例(36.43％),最常见的亚型为局灶脑动脉病(FCA,15例)和Moyamoya病(17例).婴幼儿AIS共51例(39.53％),外伤后基底节脑梗死是首要病因(24/51,47.06％),这部分患儿中21例有基底节钙化.学龄(前)儿童AIS共54例(41.86％),青少年AIS共24例(18.60％),两者均以脑动脉病为首要病因.学龄(前)儿童AIS中存在11例病因不详的患儿,均为男性,影像学椎基底动脉供血区有多个梗死灶,不能除外椎动脉夹层,但均未行颈部CTA或MRA检查.青少年AIS中2例患儿经基因检查明确诊断为腺苷酸脱氨酶2缺乏症.结论 不同年龄段儿童AIS病因存在差异,婴幼儿以外伤后基底节脑梗死最为常见,学龄(前)儿童和青少年以脑动脉病最为常见.FCA和Moyamoya病是脑动脉病中最常见的亚型.

BACKGROUND:Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is considered a demyelinating disease of the central nervous system, but an increasing number of encephalitis cases associated with MOG antibodies have been reported recently. METHODS:This was a single-center, retrospective study. All data for pediatric patients with MOGAD diagnosed at Beijing Children's Hospital from January 2017 to January 2022 were collected. Clinical characteristics and outcomes were analyzed, and treatment responses were compared between the rituximab (RTX) and mycophenolate mofetil (MMF) groups. RESULTS:A total of 190 patients (age range: 5 months to 16 years; median age: 7.2 years; females: 97) were included in this study. The phenotypes of the first attack included acquired demyelinating syndromes (105 [55%]), encephalitis other than acute disseminated encephalomyelitis (82 [43%]), and isolated meningitis (3 [2%]). After a median follow-up of 30.4 months (interquartile range: 14.8-43.7), 64 (34%) patients had relapses. Fifty-one of the 64 (80%) patients who had relapse received maintenance therapy, including MMF (41), RTX (11), maintenance intravenous immunoglobulin (two), and tocilizumab (two). The annualized relapse rates decreased significantly after treatment in both the RTX and MMF cohorts (P < 0.05); however, there were no significant differences between the two groups (P = 0.56). A total of 178 (94%) patients had complete (175 patients) or almost complete (three patients) recovery (modified Rankin scale [mRS] < 2), and 12 had moderate to severe deficits (mRS ≥ 2). CONCLUSIONS:The spectrum of pediatric MOGAD is broader than previously reported and includes demyelinating syndromes and encephalitis. Encephalitis is an important initial phenotype observed in pediatric patients with MOGAD.

Background: The variant m.3571_3572insC/MT-ND1 thus far only reported in oncocytic tumors of different tis-sues. However, the role of m.3571_3572insC in inherited mitochondrial diseases has yet to be elucidated. Methods: A patient diagnosed with MELAS syndrome was recruited, and detailed medical records were collected and reviewed. The muscle was biopsied for mitochondrial respiratory chain enzyme activity. Series of fibroblast clones bearing different m.3571_3572insC variant loads were generated from patient-derived fibroblasts and subjected to functional assays. Results: Complex I deficiency was confirmed in the patient's muscle via mitochondrial respiratory chain enzyme activity assay. The m.3571_3572insC was filtered for the candidate variant of the patient according to the guidelines for mitochondrial mRNA variants interpretation. Three cell clones with different m.3571_3572insC variant loads were generated to evaluate mitochondrial function. Blue native PAGE analysis revealed that m.3571_3572insC caused a deficiency in the mitochondrial complex I. Oxygen consumption rate, ATP produc-tion, and lactate assays found an impairment of cellular bioenergetic capacity due to m.3571_3572insC. Mito-chondrial membrane potential was decreased, and mitochondrial reactive oxygen species production was increased with the variant of m.3571_3572insC. According to the competitive cell growth assay, the mutant cells had impaired cell growth capacity compared to wild type. Conclusions: A novel variant m.3571_3572insC was identified in a patient diagnosed with MELAS syndrome, and the variant impaired mitochondrial respiration by decreasing the activity of complex I. In conclusion, the genetic spectrum of mitochondrial diseases was expanded by including m.3571_3572insC/MT-ND1.

Objectives: To investigate the clinical characteristics of the anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis with anti-myelin oligodendrocyte glycoprotein antibody(MOG-Ab)positivity serostatus in pediatric patients. Methods: The clinical manifestations, treatments, and outcomes of patients with anti-NMDAR encephalitis with positive MOG-Ab were elaborated. The annualized relapse rates (ARRs) were compared before and during treatment with disease-modifying drugs (DMDs). Results: Twelve patients were included. In the prospective cohort(Cohort A), MOG-Ab positivity was associated with relapse (p = 0.028, OR = 1.677). Eight cases relapsed, of which six cases were treated with DMDs. The median ARR reduced significantly following DMDs treatments (z = 1.992, P = 0.046). Conclusions: The anti-NMDAR encephalitis patients with MOG-Ab co-existence are prone to relapse. Long-term DMDs therapy can reduce ARRs.

ABSTRACT Introduction Primary angiitis of the central nervous system (PACNS) is a vasculitis confined to the CNS. A small proportion of the lesions may present as a tumor‐like mass, which is rarely seen in children. Case presentation A 5‐year‐old girl was admitted to our hospital because of an intermittent headache. Brain imaging suggested a space‐occupying lesion in the right cerebral hemisphere. The final diagnosis was PACNS with a lymphocytic pattern by stereotactic brain biopsy. Her condition improved after immunotherapy. Conclusion Pediatricians should consider the possibility of PACNS when encountering intracranial tumor‐like lesions. Early diagnosis of tumor‐like PACNS and prompt immunotherapy could improve the long‐term prognosis and avoid surgery.

Objective:To investigate the clinical application of the new classification criteria in children with Miller Fisher syndrome (MFS), and to analyze clinical characteristics of different types of MFS.Methods:Clinical data of MFS patients hospitalized in the Department of Neurology, Beijing Children′s Hospital, Capital Medical University from January 2015 to December 2019 were collected and analyzed retrospectively, including demographic characteristics, clinical symptoms, neurological examination findings, laboratory examination data, diagnosis and treatment, and prognosis.The counting data was described by percentage, and the measurement data was described by median.Results:A total of 23 patients were included in the research, including 14 males and 9 females, with a median age of 4 years and 8 months.There were 3 cases of pure MFS; 5 cases of incomplete MFS, including 1 case of acute ptosis and 4 cases of acute ataxia neuropathy; 15 cases of overlapping syndrome, including 13 cases of MFS/Guillain Barre syndrome (GBS), 1 case of MFS/pharyngocervical brachial variant GBS(PCB GBS)and 1 case of MFS/GBS/Bickertaff brainstem encephalitis (BBE). In addition to Ⅲ, Ⅳ and Ⅵ cranial nerve palsy, 11 cases had the involvement of other cra-nial nerves, including 2 cases in pure MFS, 8 cases in MFS/GBS and 1 case in MFS/GBS/BBE.Autonomic nervous dysfunction occurred in 6 cases.Respiratory muscle paralysis occurred in 6 cases, including 5 cases in MFS/GBS and 1 case in MFS/GBS/BBE.Graded by the Hughes scoring system (HG score), 3 cases with pure MFS were graded 4 points; 1 case with acute ptosis was graded 0; 3 cases with acute ataxia neuropathy were graded 2 points, and the other one was graded 3 points; 1 case with MFS/PCB GBS was graded 3 points; 10 cases with MFS/GBS were graded 4 points, 1 case was graded 3 points, and the other 2 cases were graded 2 points; 1 case with MFS/GBS/BBE was graded 4 points.Twenty-two patients were treated with intravenous immunoglobulin.The HG of all patients at discharge decreased at varying degree, which was graded 0 at 6 months of follow-up.Conclusions:The clinical application of the new diagnostic classification method is helpful to the accurate diagnosis of different types of MFS.More than half of MFS cases will develop into the overlapping syndrome.The overlapping of MFS and GBS or BBE is prone to the involvement of cranial nerves except for the external ophthalmic muscles, autonomic nerve dysfunction and respiratory muscle paralysis.The disease course of MFS varies, and its diagnosis should be comprehensively made.All cases of MFS in this study have a satisfactory prognosis.

Importance The phenotypes of ATP1A3 gene mutations are diverse. Relapsing encephalopathy with cerebellar ataxia and fever-induced paroxysmal weakness and encephalopathy (FIPWE) are considered non-classical phenotypes caused by p.Arg756 mutations of ATP1A3. Objective To summarize the clinical manifestations, treatment, and follow-up of Chinese patients with p.Arg756 mutations of ATP1A3. Methods We analyzed the clinical features, treatment, and genotypes of eight children with p.Arg756 mutations of ATP1A3 who were treated in Beijing Children's Hospital from January 2014 to December 2019. Results Eight patients (six boys and two girls) were included; seven had been misdiagnosed with encephalitis. The age of onset ranged from 0.8 to 4.5 years. All patients had encephalopathy and had at least one episode of FIPWE. Cerebellar ataxia was present in nine episodes. Reversible splenial lesions of the corpus callosum were found in two patients in the acute phase. Three types of heterozygous ATP1A3 mutations were found: c.2267G > T (p.R756L) (patient 3 [P3]), c.2266C > T (p.R756C) (P2 and P4), and c.2267G > A (p.R756H) (P1, P5, P6, P7, and P8). Six mutations were de novo; two mutations were inherited. Both patients with p.R756C and one patient (P7) with p.R756H had four episodes of severe ataxia as the main manifestations. However, in the other three episodes, limb weakness was more prominent than ataxia. P5 with p.R756H exhibited overlap with FIPWE and rapid-onset dystonia-parkinsonism. Interpretation Acute encephalopathy followed by febrile disease was characteristic of the disease in patients with p.Arg756 mutations of ATP1A3. However, the weakness and ataxia were variable. Phenotypic crossover and overlap were observed among these patients.

Objective: To evaluate the efficacy of mycophenolate mofetil (MMF) in the treatment of childhood MOG-IgG-associated disorder (MOGAD).Methods: Thirty patients diagnosed with relapsing MOGAD and treated with MMF for >1 year from a childhood MOGAD ambispective cohort were included in the study. The clinical characteristics, therapeutic regimen, side effects, annualized relapse rate (ARR), and Expanded Disability Status Scale (EDSS) scores of these patients were evaluated.Results: The median age of disease onset was 7.05 (2.50-12.75) years. The male to female ratio was 1:1.31. All patients used MMF as first-line maintenance treatment. The median time to add MMF from disease onset was 1.08 (0.25-5.00) year. The median number of attacks before MMF initiation was 2 (2 -8). The median duration of MMF therapy was 2.13 (1.00-3.58) years. Twenty (66.67%) patients did not experience further attacks during MMF therapy. The Kaplan-Meier curves showed a 3-year relapse-free rate of 59.8% (95% CI, 36.62-76.88%). ARR decreased during MMF therapy (0 (0 -1.72) vs. 1.25 (0.60-4.00); P < 0.05). EDSS stabilized during MMF therapy (1.0 (0 -2.0) vs. 0 (0 -2.0); P = 0.206). None of the patients stopped the use of MMF due to intolerable side effects. Onset age, sex, phenotype of the first attack, ARR before MMF, MOG-IgG titers, and combined long-term prednisone (prednisone <10 mg daily for patients >40 kg or <5 mg daily for patients <= 40 kg longer than 6 months) did not predict recurrence during MMF therapy in univariate analysis.Conclusions: MMF was effective and safe for treating childhood MOGAD. No clinical feature that could predict efficacy of MMF was found in pediatric patients with MOGAD.

Objective:To analyze the clinical and imaging features of influenza associated encephalopathy(IAE) in children, thus contributing to enhance the efficacy of early identification, timely treatment and prognosis.Methods:Clinical data, laboratory examination, imaging data, treatment and outcomes of 40 children with IAE diagnosed and treated in the Beijing Children′s Hospital, Capital Medical University from December 2016 to January 2020 were retrospectively analyzed.Clinical features were summarized and they were further classified according to clinical imaging features.The prognosis was compared and analyzed.Results:A total of 20 boys and 20 girls were recruited, with the age of attending hospital at (4.0±2.3) years (median, 3.2 years). There were 28 children with influenza A and 12 with influenza B. All children initially had fever, and the interval between fever and symptoms of neurological onset was 24 hours (0-120 hours). The most-common symptom of neurological onset was seizures(32 cases), among which 17 patients showed continuous seizures.All children presented encephalopathy at varying degrees, including 33 cases in coma and 7 in drowsiness or cognitive decline.Thirty cases developed central respiratory failure and received mechanical ventilation.Examination results showed 30 cases had elevated aspartate transaminase (AST), 18 cases had elevated alanine transaminase (ALT), 14 cases had elevated creatinine, 31 cases had elevated lactate dehydrogenase, 16 cases had elevated blood glucose and 1 case had significantly lowered blood glucose.Blood ammonia testing was performed in 38 children and 9 cases had elevated level.The whole exon sequencing in 6 cases showed de novo heterozygous mutation of the SCN1A gene in 1 case, and heterozygous mutation of the ATP1A2 gene inherited from the mother in another case.Lumbar puncture was performed in 35 cases, and all of them had a normal range of cerebrospinal fluid leukocyte counts, while 12 cases had elevated cerebrospinal fluid proteins.Abnormal image findings were examined in 33 cases and the acute necrotizing encephalopathy was the most common one (14 cases). All children received Peramivir or Oseltamivir after admission.A total of 28 cases were treated with glucocorticoids, and 29 cases were treated with immunoglobulin.Seventeen cases died, 9 cases had disability at varying degrees, and 14 cases recovered to the baseline.Patients were divided into good prognosis group and poor prognosis group.(1) Patients in good prognosis group presented significantly shorter interval between fever and first neurological symptoms[(22.7±12.2) h vs.(38.6± 30.9) h], higher Glasgow score on admission[(7.6±2.5) points vs.(4.5 ± 1.6) points], lower ALT [15.6 (9.0-1 631.5) U/L vs.140.2 (12.3-3 232.4) U/L] and lower AST [47.6 (25.4-1 721.3) U/L vs.251.8 (21.7-4 991.6) U/L] than those in poor prognosis group (all P<0.05). (2) Glucocorticoids were applied to 17 and 11 cases in good prognosis group and poor prognosis group, while immunoglobulins were applied to 17 and 12 cases, respectively ( P>0.05). (3) Patients were further classified into cytokine storm group, excitotoxicity group and unclassifiable group according to clinical imaging findings.The Glasgow score [ (4.6±1.7) points vs.(7.6±2.2) point vs.(7.3±2.8) points] and median modified Rankin Scale score (6.0 points vs.1.5 points vs.0) were significantly different among 3 groups (all P<0.01). Conclusions:Influenza associated encephalopathy is common in infants and young children.Fever, convulsions and rapidly progressing disturbance of consciousness are the most common clinical manifestations.Acute necrotizing encephalopathy is the most common subtype of clinical imaging syndrome.Acute onset and rapid progression predict the poor prognosis of influenza associated encephalopathy.

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.

Familial hemophagocytic lymphohistiocytosis Type 2 (FHL2) associated central nervous system (CNS) involvement is less understood in children, especially when considering neurologic manifestations as part of the initial presentation. We conducted a retrospective review of the clinical manifestations and genetic abnormality of four Han Chinese children with FHL2 who were patients at the neurology department of Beijing Children’s Hospital from November 2015 to October 2018. These four patients initially manifested CNS symptoms in their disease presentation, and all four patients were misdiagnosed as having ademyelinating disease, such as acute disseminated encephalomyelitis and multiple sclerosis. Given these misdiagnoses, it is important that general physicians and pediatricians maintain awareness of the possibility of FHL2 as a differential diagnosis. These four cases included neurologic manifestations including seizures, ataxia, spasticity, gait disorder, and coma. Bilateral abnormal signals in the cerebrum, including in white matter, gray matter, and junctions were discovered. Enhanced magnetic resonance imaging (MRI) in these patients showed spot or ring enhancement and/or hemorrhage. These patients all possessed a compound heterozygote mutation PRF1 gene. Whole exome sequencing analysis revealed seven different mutations (three novel mutations) spread over the PRF1 gene and a heterozygous missense mutation c.1349C > T [p.T450M] that was present in two patients. Three novel mutations, c.634T > C[p.Y212H], c.1083_1094del[p.361_364del], and c.1306G > T [p.D436Y], were discovered and through in silico analysis were discovered to be deleterious. Neurologic manifestations were the initial symptoms of FHL2 in these patients in addition to the expected leukopenia and hepatosplenomegaly. Whole exome sequencing of PRF1 for patients with similar presentations would facilitate prompt and accurate diagnosis and treatment.

OBJECTIVETo evaluate the efficacy and safety of tacrolimus in the treatment of children with myasthenia gravis (MG).METHODSA total of 28 children with MG were treated with tacrolimus. MG-Activities of Daily Living (MG-ADL) scale was used to assess clinical outcome and safety after 1, 3, 6, 9, and 12 months of treatment.RESULTSAfter tacrolimus treatment, the MG-ADL score at 1, 3, 6, 9 and 12 months was lower than that at baseline (P<0.05), and the MG-ADL score showed a gradually decreasing trend. The response rates to tacrolimus treatment at 1, 3, 6, 9, and 12 months were 59%, 81%, 84%, 88%, and 88% respectively. At 6, 9, 12, and 18 months of treatment, 4, 13, 14, and 15 children respectively were withdrawn from prednisone. No recurrence was observed during treatment. Major adverse reactions/events were asymptomatic reduction in blood magnesium in 5 children and positive urine occult blood in 1 child, which turned negative without special treatment, and tacrolimus was not stopped due to such adverse reactions/events. One child was withdrawn from tacrolimus due to recurrent vomiting. According to CYP3A5 genotypes, all of the patients were divided into two groups: slow metabolic type (n=19) and non-slow metabolic type (fast metabolic type + intermediate type; n=9). The non-slow metabolism group received a higher dose of tacrolimus, but had a lower trough concentration of tacrolimus than the slow metabolism group (P<0.05). The slow metabolism group had a higher response rates to tacrolimus treatment than the non-slow metabolism group (P<0.05).CONCLUSIONSTacrolimus appears to be effective and safe in the treatment of children with MG and is thus an option for immunosuppressive therapy. CYP3A5 genotyping has a certain guiding significance for determining the dosage of tacrolimus.

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.

Congenital myasthenic syndromes (CMSs) are a group of inherited disorders caused by genetic defects in neuromuscular junctions. Mutations in CHAT, encoding choline acetyltransferase, cause congenital myasthenic syndrome with episodic apnea (CMS-EA), a rare autosomal recessive disease characterized by respiratory insufficiency with cyanosis and apnea after infections, fever, vomiting, or excitement. To date, no studies have reported deletions comprised of multiple exons. Here, using next generation sequencing, we identified compound heterozygous mutations, namely a large maternally inherited deletion, including exons 4, 5, and 6, and a paternally inherited missense variant (c.914T>C [p.Ile305Thr]) in CHAT in a Chinese patient with a severe phenotype of CMS-EA. Furthermore, the large deletion was also validated by real-time fluorescence quantitative polymerase chain reaction. The patient was a 10-month-old boy, who presented with a weak cry and feeding difficulties soon after birth, ptosis at 4 months old, episodic apnea after fever at 9 months old, and respiratory insufficiency with cyanosis and apnea that required intubation after a respiratory tract infection at 10 months old. Unfortunately, he died in the Pediatric Intensive Care Unit soon after hospitalization. The patient's elder sister had similar clinical manifestations, and she died prior to the age of 2 months old without a diagnosis. Genotype-phenotype correlation analysis revealed that loss-of-function mutations in exons 4-6 of CHAT might cause more severe CMS-EA. To our knowledge, this is the first study to show compound heterozygous CHAT mutations consisting of a large deletion and missense mutation in a patient with CMS-EA.