Objective:To summarize the clinical manifestations, diagnosis and treatment of a family with hereditary sensory and autonomic neuropathy (HSAN) caused by the SPTLC1 gene variation and to review the literature. Methods:Case summary.The clinical manifestations, neuroelectrophysiology, genetic examination, treatment and follow-up of a family with autosomal dominant HSAN diagnosed at the Department of Neurology, Beijing Children′s Hospital in March 2024 were summarized.At the same time, related English and Chinese literatures were searched from CNKI, Wanfang and PubMed databases from their establishment to July 2024, with " serine palmitoyltransferase long-chain base subunits 1", " hereditary sensory and autonomic neuropathy", " SPTLC1" and " HSAN1" taken as key words.Results:The proband was a 11-year-and-2-month-old boy, who developed limited bending at the age of 7.The patient had ankle pain and knee bending during walking, and limited movement.He could neither jump on one foot nor bend down to pick up things from the ground, but there was no obvious sensory and autonomic nervous function abnormalities.His parents had no abnormal clinical manifestations.Neuroelectrophysiology showed peripheral nerve damage, and family whole exon sequencing revealed a maternal heterozygous missense variation of the SPTLC1 gene c.1015G>A, p.A339T(maternal origin, reported).Further maternal neuroelectrophysiology examination and sphingomyelin analysis confirmed the diagnosis of HSAN1A.The proband wore orthopedic insoles, and the proband and his mother took L-serine orally for 8 months.During the follow up, the proband reported slight improvement in muscle strength, and no adverse reactions were found.Two Chinese and thirteen English case reports on autosomal dominant HSAN caused by the SPTLC1 gene variation were retrieved.Twenty cases had complete clinical data.Therefore, a total of 22 cases, including the above-mentioned two patients, were analyzed.Except for patients whose age at diagnosis is unknown and who are deceased, the age at diagnosis ranged from 7 to 93 years.The 66.7%(14/21) cases were childhood-onset.The first clinical symptoms were mainly gait abnormalities, easy falls, sensory disorders and ulcers.Foot deformity, and autonomic neuropathy were detected in 53.3% (8/15), and 31.6% (6/19) cases, respectively, 15.8% (3/19) of the cases had amputation.Only 1 case was treated with L-serine, who showed partial relief of clinical symptoms, but electromyography was not significantly improved.Fifteen cases received neuroelectrophysiological testing, and 78.6%(11/14) of the patients showed sensory and motor neurogenic injuries.All the gene variations reported previously were missense mutations, and the high frequency variation was p. C133T/W. Conclusions:This study is helpful to improve the understanding of the clinical characteristics of HSAN1A caused by the SPTLC1 gene.Oral L-serine supplementation may benefit patients and gene detection promotes diagnosis confirmation and early treatment.

Objective:To summarize the clinical manifestations, diagnosis and treatment of a family with hereditary sensory and autonomic neuropathy (HSAN) caused by the SPTLC1 gene variation and to review the literature. Methods:Case summary.The clinical manifestations, neuroelectrophysiology, genetic examination, treatment and follow-up of a family with autosomal dominant HSAN diagnosed at the Department of Neurology, Beijing Children′s Hospital in March 2024 were summarized.At the same time, related English and Chinese literatures were searched from CNKI, Wanfang and PubMed databases from their establishment to July 2024, with " serine palmitoyltransferase long-chain base subunits 1", " hereditary sensory and autonomic neuropathy", " SPTLC1" and " HSAN1" taken as key words.Results:The proband was a 11-year-and-2-month-old boy, who developed limited bending at the age of 7.The patient had ankle pain and knee bending during walking, and limited movement.He could neither jump on one foot nor bend down to pick up things from the ground, but there was no obvious sensory and autonomic nervous function abnormalities.His parents had no abnormal clinical manifestations.Neuroelectrophysiology showed peripheral nerve damage, and family whole exon sequencing revealed a maternal heterozygous missense variation of the SPTLC1 gene c.1015G>A, p.A339T(maternal origin, reported).Further maternal neuroelectrophysiology examination and sphingomyelin analysis confirmed the diagnosis of HSAN1A.The proband wore orthopedic insoles, and the proband and his mother took L-serine orally for 8 months.During the follow up, the proband reported slight improvement in muscle strength, and no adverse reactions were found.Two Chinese and thirteen English case reports on autosomal dominant HSAN caused by the SPTLC1 gene variation were retrieved.Twenty cases had complete clinical data.Therefore, a total of 22 cases, including the above-mentioned two patients, were analyzed.Except for patients whose age at diagnosis is unknown and who are deceased, the age at diagnosis ranged from 7 to 93 years.The 66.7%(14/21) cases were childhood-onset.The first clinical symptoms were mainly gait abnormalities, easy falls, sensory disorders and ulcers.Foot deformity, and autonomic neuropathy were detected in 53.3% (8/15), and 31.6% (6/19) cases, respectively, 15.8% (3/19) of the cases had amputation.Only 1 case was treated with L-serine, who showed partial relief of clinical symptoms, but electromyography was not significantly improved.Fifteen cases received neuroelectrophysiological testing, and 78.6%(11/14) of the patients showed sensory and motor neurogenic injuries.All the gene variations reported previously were missense mutations, and the high frequency variation was p. C133T/W. Conclusions:This study is helpful to improve the understanding of the clinical characteristics of HSAN1A caused by the SPTLC1 gene.Oral L-serine supplementation may benefit patients and gene detection promotes diagnosis confirmation and early treatment.

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.

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.

Objective:To summarize the clinical characteristics of SYNGAP1-related epilepsy in children.Methods:Data of 13 patients with SYNGAP1 gene variants diagnosed with epilepsy at Department of Neurology, Beijing Children's Hospital were collected retrospectively from March 2017 to October 2020 and the patients were followed up. The clinical features, electroencephalogram(EEG), brain imaging, gene results and treatment were summarized.Results:Twelve patients were followed up successfully among the 13 patients with SYNGAP1 variants. The last follow-up age was 5 years and 7 months (3 years and 1 month to 9 years).The onset age of seizures was 2 years (4 months to 3 years). Seizure types included eyelid myoclonia with or without absence (9 cases), myoclonic seizure (5 cases), atypical absence (4 cases), suspicious atonic seizures(4 cases),unclassified fall attack (6 cases), and the frequency of seizures varied from several times to more than 100 times per day. Four cases had the mimic phenotype of myoclonic astatic epilepsy. The seizures of 10 cases could be triggered by eating (5 cases), emotion (5 cases), fever (3 cases), voice (2 cases), fatigue (2 cases), etc. Electroencephalography (10 cases) showed interictal generalized or focal epileptiform discharges (9 cases), and atypical aphasia (4 cases), myoclonic seizure (2 cases) and eyelid myoclonic seizure (1 case) were monitored. Of the 12 cases, 9 were added with valproate, all of which were effective (the frequency of seizures reduced>50%). Five cases received combined levetiracetam, in 3 the treatments were effective. To last follow-up, 3 cases were seizure free from 6 months to 1 year and 1 month, but the remaining 7 cases still had seizures, one or several times per day. All 13 cases had developmental retardation (speech ability impaired mostly), 2 cases were severe, 10 cases were moderate, 1 case was mild. The SYNGAP1 gene variants of 13 patients were all de novo, including 12 variants. Among them, 4 were frameshift variants, 4 were nonsense variants, 2 were missense variants and 2 were splice site variants.Conclusions:Patients with SYNGAP1-related epilepsy have an early onset age and many seizure types. The main seizure type is eyelid myoclonia with or without absence, and other seizure types include myoclonic seizure, atypical absence, unclassified fall attack, etc. Valproate is effective in most patients, but seizures in some patients might be intractable. Most patients have developmental delay (mainly moderate and severe), speech ability impaired mostly.

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.

Objective:To investigate the clinical features, imaging findings and prognosis of children with overlapping syndrome of myelin oligodendrocyte glycoprotein (MOG) antibody disease and anti-N-methyl-D aspartate receptor (NMDAR) encephalitis (MNOS).Methods:The clinical manifestations, immunological antibodies in blood and cerebrospinal fluid, cranial image, treatment and follow-up of 11 patients diagnosed as MNOS in the Department of Neurology, Beijing Children′s Hospital from January 2011 to April 2019 were analyzed retrospectively.Results:A total of 11 patients, including 4 males and 7 females were analyzed, the age of onset was (10.4±2.3) years. A total of 29 episodes occurred in 11 children. At the last follow-up, 8 cases showed relapsed remission course, the interval of recurrence was 3 to 60 months. The onset symptoms of 11 patients included convulsions (10 cases), lethargy (6 cases), psychosis (6 cases). Among 29 episodes, the common symptoms were convulsions (16 episodes), psychosis (13 episodes),and lethargy (10 episodes). According to the diagnostic criteria of anti-NMDAR encephalitis and MOG-antibody disease, 29 episodes were divided into three phenotypes, including anti-NMDAR encephalitis(4 episodes), MOG-antibody diseases (10 episodes) and overlapping types (15 episodes).Twenty-seven times of acute stage cranial magnetic resonance imaging (MRI) were available, common lesions included cortical focus (22 times), subcortical white matter (7 times), brainstem (9 times). All patients were sensitive to first-line immunotherapy. Eight patients had recurrence during glucocorticoid reduction, 6 of them were treated with additional second-line immunosuppressive therapy, including cyclophosphamide (1 case) and mycophenolate mofetil (5 cases). The follow-up time of patients were 5-99 months. At the last follow-up, all patients were in remission, the pediatric cerebral performance category (PCPC) score was 1 (10 cases) and 2 (1 cases).Conclusions:MNOS mainly affects older children. In the period of acute episodes, convulsions and psychosis are common. The cranial MRI showed extensive brain involvement and mainly in the cortex. The recurrence rates of MNOS are relatively high, patients are sensitive to first-line immunotherapy. No significant neurological dysfunction was left in the remission stage.

Objective: To characterize fever-induced paroxysmal weakness and encephalopathy (FIPWE) caused by ATP1A3 gene pathogenic variant. Methods: Phenotypic and genotypic characteristics of 4 FIPWE patients (3 boys and 1 girl), who were ascertained from October 2016 to March 2018 in Beijing Children's Hospital due to ATP1A3 heterozygous variants, were retrospectively analyzed. The whole exsome sequencing was used for genetic testing. Results: The onset ages of 4 patients were 2 years and 9 months, 2 years and 4 months, 8 months, 2 years and 5 months respectively. The episode ranged from 1 to 3 times, and at 3 months to 2 years and 10 months intervals. All 4 patients had symptoms of limb weakness and encephalopathy, accompanied with mild to severe ataxia or athetosis. The tendon reflex was absent in all patients, and the Babinski's sign was positive. Three patients had dysphagia and 3 patients had slurred speech. Three patients had abnormal eye movements, including strabismus and opsoclonus. None of the 4 patients exhibited visual impairment, auditory impairment or talipes cavus. The duration of acute phase ranged from 1 week to 3 months. In 3 relapsing patients, symptoms became progressively worse, with relapses occurring frequently and recovery being more difficult, and various sequelae were found after the last relapse. All patients carried heterozygous variant in ATP1A3 gene. The missense variants result in the substitution of an arginine residue at position 756. Three variants were identified, including C. 2267G > T (p. R756L) (1 case), C. 2266C > T (p. R756C) (2 cases), and C. 2267G > A (p. R756H) (1 case). Three were de novo and one inherited from his father, but the grandparents did not carry the variant. All variants were reported as pathogenic. Conclusions FIPWE is one of new clinical phenotypes of ATP1A3 spectrum disease and most cases are sporadic. The missense variants result in the substitution of an arginine residue at position 756. This report provided insights into the phenotype-genotype association in patients with FIPWE caused by pathogenic variants of ATP1A3.

Objective: To investigate the clinical significance of different samples (the peripheral blood, urine and skeletal muscle) that could be detected the large-scale single deletions directly by using next-generation sequencing in the diagnosis of Kearns-Sayre syndrome (KSS) by concluding the clinical and genetic features of KSS, in order to explore a non-invasive method for diagnosis. Methods: The clinical data, skeletal muscle′s pathology and enzymology and genetic results of individuals with KSS, who were hospitalized from October 2016 to October 2017 in Department of Neurology, Beijing Children′s Hospital, Capital Medical University, were collected.The gene tests were performed by using next generation sequencing technology and long-PCR technology of mitochondrial DNA(mtDNA) and the whole exon in the peripheral blood, urine and skeletal muscle. Results: Four patients were all consistent with the diagnosis criteria of KSS, among whom the age of onset was 8.2 years old on average, and the initial symptoms were statue, ptosis, headache and vomiting, and visual impairment.The common symptoms of the 4 cases were ophthalmoplegia, exercise intolerance, development delay, loss of appetite, hypotonia, muscle weakness, with cerebrospinal fluid protein concentration over 1 000 mg/L, the cerebral magnetic resonance imaging showed that abnormal signals in the brainstem, in addition, white matter, thalamus, basal ganglia, cerebrum and cerebellum atrophy could be found.Moreover, 3 cases had cardiac conduction block.Two cases had maternal family history.Molecular analysis of the 4 cases revealed the large-scale single deletions of mtDNA from the peripheral blood, the urine, the skeletal muscle through the next-generation sequencing, which were m. 6460-15590(9 131 bp del), m.8482-13446(4 964 bp del), m.6831-14981(8 151 bp del), m.7983-15495(7 513 bp del), respectively.Among 3 cases who did pedigree analysis, only the mother of case 4 was detected with the same variation of the proband. Conclusions KSS is a rare mitochondrial disease, which could be detected with the single large scale mtDNA deletions in the peripheral blood, urine and skeletal muscle.With the development of the methodology, the diagnosis of KSS maybe no longer than depends on the muscle biopsy with the next-generation sequencing.And the possibility to get the positive results in the peripheral blood and urine by the non-invasive method could improve the molecular diagnosis of KSS.