Objective:To summarize the clinical and prognostic features of children with opsoclonus-myoclonus-ataxia syndrome (OMAS).Methods:A total of 46 patients who met the diagnostic criteria of OMAS in the Department of Neurology, Beijing Children′s Hospital from June 2015 to June 2023 were retrospectively analyzed. Centralized online consultations or telephone visits were conducted between June and August 2023. The data of the children during hospitalization and follow-up were collected, including clinical manifestations, assistant examination, treatment and prognosis. According to the presence or absence of tumor, the patients were divided into two groups. The chi-square test or Mann-Whitney U test was used to compare the differences between the two groups. Univariate Logistic regression was used to analyze the factors related to OMAS recurrence and prognosis. Results:There were 46 patients, with 25 males and the onset age of 1.5 (1.2, 2.4) years. Twenty-six (57%) patients were diagnosed with neuroblastoma during the course of the disease, and no patients were categorized into the high-risk group. A total of 36 patients (78%) were followed up for≥6 months, and all of them were treated with first-line therapy with glucocorticoids, gammaglobulin and (or) adrenocorticotrophic hormone. Among the 36 patients, 9 patients (25%) were treated with second-line therapy for ≥3 months, including rituximab or cyclophosphamide, and 17 patients (47%) received chemotherapy related to neuroblastoma. At the follow-up time of 4.2 (2.2, 5.5) years, 10 patients (28%) had relapsed of OMAS. The Mitchell and Pike OMS rating scale score at the final follow-up was 0.5 (0, 2.0). Seven patients (19%) were mildly cognitively behind their peers and 6 patients (17%) were severely behind. Only 1 patient had tumor recurrence during follow-up. The history of vaccination or infection before onset was more common in the non-tumor group than in the tumor group (55%(11/20) vs. 23%(6/26), χ2=4.95, P=0.026). Myoclonus occurred more frequently in the non-tumor group (40%(8/20) vs. 4%(1/26), χ2=7.23, P=0.007) as the onset symptom. Univariate Logistic regression analysis showed that the tumor group had less recurrence ( OR=0.19 (0.04-0.93), P=0.041). The use of second-line therapy or chemotherapy within 6 months of the disease course had a better prognosis ( OR=11.64 (1.27-106.72), P=0.030). Conclusions:OMAS in children mostly starts in early childhood, and about half are combined with neuroblastoma. Neuroblastoma in combination with OMAS usually has a low risk classification and good prognosis. When comparing patients with OMAS with and without tumors, the latter have a more common infection or vaccination triggers, and myoclonus, as the onset symptom, is more common. Early addition of second-line therapy is associated with better prognosis in OMAS.

Objective:To investigate the clinical characteristics, laboratory characteristics and genetic diagnosis of aromatic L-amino acid decarboxylase deficiency (AADCD), and to improve the understanding of this disease.Methods:Four children diagnosed with AADCD from the Department of Neurology, Beijing Children′s Hospital Affiliated to Capital Medical University from August 2016 to June 2020 were collected, and their clinical manifestations, laboratory and imaging data, and genetic test results were retrospectively analyzed.Results:All the 4 cases were diagnosed in early infancy, with the first symptom of feeding difficulties. They developed paroxysmal dyspraxia accompanied by eye movement crisis, movement regression, hypotonia, growth retardation, sleep disorders and autonomic nervous symptoms such as ptosis, excessive sweating and nasal congestion at the age of 2-4 months, respectively. The 4 children were siblings from 2 families with healthy parents. The dihydroxyphenylalanine decarboxylase ( DDC) gene mutations in cases 1 and 2 were derived from the maternal missense mutation c.1040G>A(P.RG347gln), and from the paternal deletion of exons 11 and 12, respectively. The DDC gene mutation in case 3 was derived from the maternal mutation c.419G>A(p.G140E) and the paternal mutation c.1375C>T(p.H459Y), respectively. Case 4 did not undergo genetic testing. Blood amino acid and acylcarnitine profiles and urine organic acid analyses were performed in 3 cases, and no specific abnormalities were found. In case 3, the results of 3-O-methyldopa (3-OMD) screening by blood dry filter paper increased significantly. Cerebrospinal fluid neurotransmitter detection results showed that the concentrations of 3-methoxy-4-hydroxyphenyldiol, vanillic acid and 5-hydroxyindoleacetic acid were significantly decreased, while the levels of 5-hydroxytryptophan and 3-OMD were increased in case 3. Blood aromatic L-amino acid decarboxylase (AADC) activity decreased significantly in case 3. Cranial magnetic resonance imaging (MRI) and electroencephalogram (EEG) examinations were performed in cases 1, 3, and 4, among which the cranial MRI in case 1 was normal, while the cranial MRI in cases 3 and 4 suggested that myelination was slightly backward. The EEG was normal in all the 3 cases. Cases 1 and 2 died of pneumonia and respiratory failure at the age of 1 year and 10 months. Case 3 was given clonazepam, benxel hydrochloride tablets and vitamin B6 tablets orally after diagnosis at the age of 4 months, and then treated with selegiline hydrochloride tablets and pramexol hydrochloride tablets. At the follow-up of 1 year and 6 months, the frequency of eye movement crisis and movement disorder was reduced, sleep was improved and autonomic nervous symptoms were alleviated, but there was no improvement in developmental delay. Case 4 was diagnosed with cerebral palsy and epilepsy, but failed various antiepileptic drugs and rehabilitation training, and died at the age of 10 due to heart failure and kidney failure. Conclusions:The clinical manifestations of AADCD are complicated and the misdiagnosis rate is high. Infants with early-onset hypotonia, developmental retardation, eye movement crisis, and movement disorders should be screened with dry filter paper as soon as possible for 3-OMD level, and suspicious cases should be diagnosed by cerebrospinal fluid neurotransmitter detection, plasma AADC activity determination, and gene examination. Early diagnosis of AADCD in children and gene mutation carriers can guide treatment and provide genetic counseling to reduce the incidence of the offspring.

The male patient of middle-age was admitted to Zhujiang Hospital, Southern Medical University on September 5, 2020, due to wear and rupture of the left foot hallux for more than 10 days, gradually developed swelling and blackening of the left foot and accompanied by drowsiness for 1day. Results from etiological examination of his wound secretions suggested the mixed infection of Wohlfahrtiimonas chitiniclastica and Enterococcus faecalis. The disease progressed rapidly and the patient still died of septic shock after anti-infective treatment. The infection of W. chitiniclastica is rare and has a great relationship with poor hygiene and chronic open wounds. It is necessary to use matrix-assisted laser desorption/ionization-time of flight mass spectrometry or 16S ribosomal RNA gene sequencing for strain identification. Moreover, it is recommended to use cephalosporins or carbapenems as first-line drugs due to the poor prognosis of patients with bloodstream infections.

The CACNA1A gene encodes a voltage-gated calcium channel of the pore-forming protein, which has important functions in the central nervous system.The CACNA1A gene mutation can lead to a variety of neurological diseases, including familial hemiplegic migraine 1, spinocerebellar ataxia 6, episodic ataxia 2 and early infantile epileptic encephalopathy 42.Overlapping phenotypes could be observed in a small number of patients.This review summarized the clinical and genetic characteristics of the CACNA1A gene mutation.

Objective:To summarize the clinical characteristics of children with dystonia 28 (DYT28) caused by KMT2B gene variations so as to improve clinicians′ understanding of the disease. Methods:The clinical manifestations, treatment and gene variation data of 11 children with DYT28 caused by KMT2B gene variations were retrospectively collected and analyzed.The subjects were recruited from the Department of Neurology, Beijing Children′s Hospital, Capital Medical University from March 2018 to January 2021.The patients were followed up. Results:There were 8 males and 3 females.The age at onset was ranging from 1 month to 6 years without inducement.Eight cases were gene-ralized dystonia and 3 cases were multifocal dystonia.The initial symptoms of 7 cases were unilateral or bilateral lower limbs tiptoeing.Four cases presented dysarthria, retching or swallowing difficulties at onset.As the disease progressed, all the cases had laryngeal dystonia, 10 cases had lower limbs dystonia, and 8 cases had upper limbs dystonia.Six cases were complicated with other dyskinesia symptoms.Ten cases had varying degrees of short stature, microcephalus, micrognathia, musculoskeletal abnormalities, intellectual disability, endocrinopathies and sleep difficulties.The brain magnetic resonance imaging showed abnormal in only 1 case.Eleven KMT2B gene pathogenic variants were found, including 8 frameshift variants, 1 in-frame variant and 2 missense variants.Four variants were novel.Eleven cases were followed up at the age of 1 year and 7 months to 17 years and 9 months.One case wasn′t given therapy.The dystonia in 3 cases was mildly improved after medication.Dysfunction of urination and defecation was disappeared in 1 case after medication.The symptom of 6 cases had no improvement after drug therapy.Among the above 6 cases, 5 drug refractory cases had deep brain stimulation, and their dystonia symptoms are all obviously improved; 2 cases had normal control of urination and defecation after deep brain stimulation.The motor scores in the Burke-Fahn-Marsden dystonia rating scale were improved by 55.8%-90.7%, and the disability scores were improved by 14.8%-69.6%. Conclusions:DYT28 caused by KMT2B gene variations is one of the most common and early-onset genetic dystonia in children.The dystonia symptom progresses from local parts to the whole body, prominently involving laryngeal muscles and lower limbs.Control of urination and defecation requires attention.Patients with mild dystonia symptoms can be effectively treated by drugs.However, patients with severe dystonia symptoms were drug refractory, and their dystonia symptoms can be effectively improved by deep brain stimulation.

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 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.