1.Function disability evaluation in hereditary motor and sensory neuropathy pediatric patients
Chinese Journal of Applied Clinical Pediatrics 2014;29(12):945-947
Hereditary motor and sensory neuropathy is the most common peripheral neuropathy.It is slowly progressive,proximal limb weakness and muscular dystrophy and severe foot deformity can cause function disability.For most patients were diagnosed in early children,so function disability evaluation and effective treatment from children is significant to their prognosis.
2.Clinical characteristics and follow-up of pediatric patients with neuromyelitis optica and neuromyelitis optica spectrum disorders.
Wu YUN ; Zhang WEIHUA ; Ren XIAOTUN ; Li JIUWEI ; Yang XINYING ; Lyu JUNLAN ; Ding CHANGHONG ; Chen CHUNHONG ; Ren HAITAO ; Cui LIYING ; Fang FANG
Chinese Journal of Pediatrics 2015;53(4):268-273
OBJECTIVETo analyze the clinical characteristics of pediatric neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorders (NMOSD).
METHODA retrospective analysis was performed evaluating clinical and laboratory characteristics of ten NMO and NMOSD children who were seen in our hospital from December 2010 to May 2014. Median age at onset was 8.9 years (range 0.8-13.8 years). Seven cases were female and three were male. Median disease duration was 1.5 months (range 1-18.5 months).
RESULTEight patients fulfilled diagnostic criteria for NMO and two patients fulfilled diagnostic criteria for NMOSD. The two NMOSD patients had recurrent longitudinally extensive transverse myelitis. Four cases had a monophasic disease course, and six cases had a recurrent course. In eight NMO patients, neuritis was the initial presentation. The two NMOSD patients had no neuritis in the first attack. Nine cases had clinical manifestations of myelitis, one case had asymptomatic spinal cord MRI anomaly. Among the ten patients, seven cases had brain lesions, wherein, four cases had the midbrain involvement and in four cases extensive hemispheric white matter was involved. Three cases had medullary involvement. And two cases had posterior limb of the internal capsule involvement, two cases had thalamus involvement. In one case there was pons, cerebellum or corpus callosum involvement, respectively. One case had accompanied brain symptoms. Of the five patients who had symptomatic brain lesions, four cases had encephalopathy accompanied by large hemispheric lesions on MRI, having a presentation similar to acute disseminated encephalomyelitis. And one case had multiple sclerosis like brain lesion. Of the ten patients tested, nine were seropositive for anti-aquaporin-4 autoantibody. One-patient was complicated with systemic lupus erythematosus. Oligoclonal bands were negative in all cases. All patients received treatment for acute attacks with high-dose intravenous methylprednisolone and intravenous gammaglobulin. The symptoms of 8 cases mitigated. Two cases whose symptoms showed no sign of improvement received plasmapheresis for acute attacks. Seven of the patients were followed up. The median duration of follow-up was 19 months (ranged from 13 months to 30 months). The median Expanded disability status (EDSS) score was 3 (range 1-7).
CONCLUSIONPediatric NMO and(or) NMOSD have a diverse clinical presentation which are more than just optic neuritis and transverse myelitis, including brain symptom. So it may be difficult to distinguish NMO and( or) NMOSD from acute disseminating encephalomyelitis and multiple sclerosis in the early stages of the disease. Antibodies to aquapoin-4 (AQP-Ab) testing is very important for differential diagnosis.
Adolescent ; Anti-Inflammatory Agents ; therapeutic use ; Aquaporin 4 ; Autoantibodies ; Brain ; Brain Diseases ; Child ; Child, Preschool ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Infant ; Magnetic Resonance Imaging ; Male ; Methylprednisolone ; therapeutic use ; Multiple Sclerosis ; etiology ; Neuromyelitis Optica ; complications ; diagnosis ; drug therapy ; Retrospective Studies
3.Clinical features and genetic characteristics of children with tyrosine hydroxylase deficiency caused by TH gene variants
Lifang DAI ; Changhong DING ; Fang FANG ; Weihua ZHANG ; Ming LIU ; Xiaojuan TIAN ; Xiaotun REN ; Xiaohui WANG ; Jiuwei LI ; Xiuwei ZHUO ; Shen ZHANG ; Junlan LYU ; Husheng WU
Chinese Journal of Applied Clinical Pediatrics 2021;36(8):574-579
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.
4. Phenotypic and genotypic characteristics of fever-induced paroxysmal weakness and encephalopathy caused by ATP1A3 pathogenic variants
Weihua ZHANG ; Xiaotun REN ; Weixing FENG ; Chunhong CHEN ; Changhong DING ; Junlan LYU ; Tongli HAN
Chinese Journal of Pediatrics 2019;57(7):543-547
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.
5.A case report and literature review of myocardial hypertrophy in children's acute rhabdomyolysis
Qirui LI ; Yue YUAN ; Haoxun TANG ; Lang CUI ; Lu GAO ; Junlan LYU
Chinese Journal of Applied Clinical Pediatrics 2014;29(1):48-51
Objective To report one case of the children's acute rhabdomyolysis(RM) with myocardial hypertrophy for the first time and the related data in order to improve the clinical diagnose and the treatment efficacy.Methods Clinical data of the patient with myocardial hypertrophy and pericardial effusion treated in the Heart Center of Beijing Children's Hospital Affiliated to Capital Medical University were retrospectively analyzed.According to the symptoms,signs,laboratory examination,the diagnosis was made and related literature was reviewed.Results A 7-years-old girl was characterized by myalgia,weakness,and dark urine.Physical examination showed extremity swelling,clammy skin,lower extremity muscle tenderness positive.Creatine kinase (CK) and myoglobin levels increased.So she was clearly diagnosed of acute RM undoubtedly.Without physical,metabolic and autoimmune factors,the patient was only had positive mycoplasma antibodies and might be coursed by mycoplasma infection.The muscular involvement was so severe that the patient had the heart failure,myocardial hypertrophy and pericardial effusion was conformed to ultrasound cardiogram(UCG).After treatment with hydration,alkalization,anti-infection,support and symptomatic therapy for a few days,the clinical symptoms improved obviously,CK returned to normal,myocardial hypertrophy and pericardial effusion disappeared.One-year-follow-up study indicated that the child's animal force and body movements were norrmal,and CK and UCG were negative.Conclusions Acute RM is a rare disorder and less recognized in children,and myocardial hypertrophy and pericardial effusion may be caused by acute RM.If the diagnosis and treatment are done earlier,the prognosis will be good,without permanent complications.
6.Diversity and antimicrobial susceptibility of cultivable commensal bacteria from 18 to 22 year-old healthy people's nose and skin
Hongwei MENG ; Yao LIU ; Junlan LIU ; Huiying LYU ; Yihui XIE ; Qian LIU ; Min LI
Chinese Journal of Laboratory Medicine 2018;41(3):196-202
Objective To investigate the diversity and antimicrobial susceptibility of cultivable commesal bacteria from 18 to 22 year-old healthy people′s nose and skin. Methods From June to August 2017,18 to 22 year-old healthy people (n=210) were swabbed on skin and nose and cultured with blood plates at Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Species determination was performed using matrix assisted laser desorption Lonization-time of flight-mass spectrometry(MALDI-TOF-MS);Susceptibility testing was performed on the major species by the disc diffusion method; Genomic characteristics of methicillin resistant Staphylococcus epidermidis(MRSE) were determined by pulsed field gel electrophoresis (PFGE) method;SCCmec typing was tested by polymerase chain reaction(PCR);Statistical analysis was performed using SPSS software and association statistics were tested using Chi-Square tests. Results In total, 25 genera were identified of cultivable bacteria from 210 healthy people′s nose (1497 isolates) and skin (941 isolates).Staphylococcus isolates from nose and skin accounted for 82.03% and 80.23% respectively.Eleven species were identified of all Staphylococcus isolates and coagulase-negative Staphylococci(CoNS)from nose and skin accounted for 90.72% and 99.21% respectively.Furthermore, a variety of other species and differences between men and women were observed. Susceptibility testing was done on 631 Staphylococcus isolates, which were sensitive to most antibiotics but show high prevalence of resistance towards penicillin (76.55%), erythromycin (41.20%), clindamycin (10.77%) and trimethoprim/sulfamethoxazole(10.14%). Methicillin Resistant Staphylococcus (MRS) (45 isolates) showed higher prevalence of resistance towards penicillin (χ2=12.17,P<0.001), erythromycin (χ2=10.80,P=0.001), levofloxacin (χ2=20.24, P<0.001) and trimethoprim/sulfamethoxazole (χ2=58.57,P<0.001) compared to methicillin sensitive Staphylococcus (MSS)(586 isolates). Moreover, multidrug resistance (MDR) was observed in 42.16% of 631 isolates and MRS showed a significantly higher proportion than MSS(100.00% vs 37.71%,χ2=66.49,P<0.001).PFGE generated 23 groups out of 33 MRSE isolates. SCCmec genotyping of MRSE showed the most prevalent type was SCCmecⅣ (66.67%). Conclusions Obvious genus and species diversity and genetic diversity were observed on cultivable bacteria from 18 to 22 year-old healthy people′s nose and skin,and CoNS was in the majority. Staphylococcus isolates from healthy people′s nose and skin were sensitive to most antibiotics,but show high prevalence of resistance towards penicillin, erythromycin, clindamycin and trimethoprim/sulfamethoxazole. In addition, MDR was serious especially in MRS. Commensal bacteria may act as reservoir for resistance genes facilitating bacteria infection.
7.Clinical features and gene diagnosis of L-2-hydroxyglutaric aciduria in 4 children
Hong JIN ; Xiaotun REN ; Xiaohui WANG ; Chunhua ZHANG ; Xu WANG ; Junlan LYU ; Weihua ZHANG ; Husheng WU ; Fang FANG
Chinese Journal of Applied Clinical Pediatrics 2018;33(16):1258-1262
Objective To investigate the clinical features and gene diagnostic bases of childhood L-2 -hydroxyglutaric aciduria (L-2-HGA). Methods The clinical data involving manifestations,laboratory examinations of 4 children with L-2-HGA admitted to Beijing Children′s Hospital Affiliated to Capital Medical University from April 2015 to March 2018 were retrospectively analyzed. Each patient had a follow-up visit ranging from 3 months to 3 years and 2 months after initial examination. Results The 4 patients,of whom 2 were siblings,consisted of 1 male and 3 females,whose age of onset ranged from 8 months old to 3 years old. All of them presented with seizures as their initial symptom. The developmental milestones were all normal before onset,while 3 cases gradually became mentally stagnant. Other symptoms included unsteady gait in 3 cases,slight hand trembling when holding items in 2 cases,and pyramidal impairment in 2 cases. Bilateral symmetric abnormalities in subcortical white matter,basal ganglia and dentate nucleus were detected by cranial magnetic resonance imaging (MRI)in all patients,and cerebral and cerebellar atrophy was ob-served in 1 case. Organic acid analysis by gas chromatography/ mass spectrometry (GC/ MS)demonstrated notable ele-vation of urinary 2-hydroxyglutaric acid in 3 cases. Pathogenic mutations on L2HGDH gene were detected by target -capture high-throughput sequencing in all 4 patients. The compound heterozygous mutations of c. 845G > A (p. Arg282Gln)and c. 800_801delCA (p. Ser267Ter)were identified in case 1,the homozygous missense mutation of c. 584A > G (p. Tyr195Cys ) in case 2 and case 3,and the homozygous frameshift mutation of c. 407delA (p. Lys136SerfsTer3)in case 4. The variants of c. 800_801delCA and c. 407delA were novel mutations firstly reported in this study. Sanger sequencing verified that parents of the 4 cases were all heterozygous carriers. The follow-up study in 2 cases who were put on high dosage of vitamin B2 and L-carnitine had shown a relatively favorable outcome of mild remission in ataxia and absence of mental degradation and further seizures,while the other 2 cases without specific therapy remained relatively stable. Conclusions The main clinical manifestations of L-2-HGA are mental retarda-tion,seizures and ataxia. Bilateral symmetric abnormalities in subcortical white matter,basal ganglia and dentate nucleus are specific neuroimaging findings. Significant elevation of urinary 2-hydroxyglutaric acid is the basic feature of the disease,while gene assessment should be the gold standard in the diagnosis of L-2-HGA. Treatment with high dosage of vitamin B2 and L-carnitine might be effective to partial patients.
8. Clinical features and diagnosis of childhood leukoencephalopathy with cerebral calcifications and cysts in four cases
Hong JIN ; Husheng WU ; Changhong DING ; Zhen JIN ; Yu HUANG ; Chunju ZHOU ; Weihua ZHANG ; Junlan LYU ; Lifang DAI ; Xiaotun REN ; Ming GE ; Fang FANG
Chinese Journal of Pediatrics 2018;56(7):539-544
Objective:
To investigate the clinical features and diagnostic bases of childhood leukoencephalopathy with cerebral calcifications and cysts (LCC).
Methods:
The clinical data involving manifestations and laboratory examinations of 4 children with LCC admitted to Beijing Children's Hospital Affiliated to Capital Medical University from 2012 to 2017 were retrospectively summarized. Each patient had a follow-up visit ranging from 4 months to 5 years and 9 months after initial examination.
Results:
Patients consisted of 2 males and 2 females, whose age of onset was respectively 2 years and 9 months, 6 years and 2 months, 7 years and 10 months, and 5 years and 1 month. The main clinical symptoms of these cases included headache, dizziness, partial seizure and claudication, and two of these cases had insidious onset. Cerebral calcifications and cysts with leukoencephalopathy were detected by neuroimaging in all patients. In addition, multifocal microhemorrhages and calcifications were observed by magnetic susceptibility-weighted imaging (SWI) series in 3 patients. Brain biopsy performed on 1 case disclosed a neuronal reduction in the cerebral cortex, loosening of focal white matter, multifocal lymphocyte infiltration, fresh hemorrhages, and gliosis, as well as angiomatous changes of blood vessels with hyalinized thicken-wall, stenotic or occlusive lumina and calcification deposits. The compound heterozygous mutations of n.*10G>A and n.82A>G in SNORD118 were identified in 1 case by target-capture next-generation sequencing. Sanger sequencing verified that the variant n.*10G>A was a novel mutation and it was of paternal-origin, while the variant n.82A>G was of maternal-origin, which had already been reported to be pathogenic to LCC. Follow-up study had shown continued partial seizure in 1 case and remissive claudication in another, while the remaining 2 cases had a relatively favorable outcome without obvious neurological symptoms at present time.
Conclusions
The clinical manifestations of LCC are nonspecific, and the onset of the disease tends to be insidious. The triad neuroimaging findings of cerebral calcifications, cysts and leukoencephalopathy are essential to the diagnosis of the disease, and the signals of microhemorrhages revealed by SWI series provide another eloquent reference for the diagnosis. As biopsy is invasive and usually unavailable in the early stage, gene assessment, instead of pathological data, should be the gold standard in the diagnosis of LCC.
9. Clinical characteristics and genetic features of benign infantile epilepsy with PRRT2 mutation
Chunhong CHEN ; Husheng WU ; Xiaohui WANG ; Hongmei WANG ; Shen ZHANG ; Junlan LYU ; Xiaotun REN ; Fang FANG ; Guohong CHEN
Chinese Journal of Pediatrics 2018;56(11):818-823
Objective:
To summarize the detailed clinical characteristics and genetic features of benign infantile epilepsy with PRRT2 mutation, in order to improve the understanding of the disease.
Methods:
The clinical data and genetic results of 40 benign infantile epilepsy patients with PRRT2 mutation who were diagnosed and treated in the neurology department of National Center for Children's Health (Beijing) , Beijing Children's Hospital affiliated to Capital Medical University from January 2002 to October 2017 and their affected family members were analyzed.
Results:
Forty benign infantile epilepsy patients were recruited for this study, with 18 males and 22 females. The age at onset ranged from 3 to 15 months (median: 4.6 months). All patients presented focal seizures with or without secondary generalization. Decreased responsiveness, eyes stare and cyanosis were commonly observed. A cluster of seizures was observed in 20 patients at the beginning of the disease, but interictal clinical conditions were normal. Interictal electroencephalograms were normal in 32 cases but 8 cases showed small amount scattered spike and spike wave. Two patients developed paroxysmal kinesigenic dyskinesia in 30 months and 12 years respectively after the cessation of the seizure. Thirty-four affected pedigree members had a history of paroxysmal episodes in 24 families, including 19 individuals of infantile afebrile convulsion, 6 individuals of paroxysmal kinesigenic dyskinesia during childhood or adulthood, 8 individuals of infantile convulsion and paroxysmal kinesigenic dyskinesia during adulthood, one individual of infantile febrile convulsion. The follow-up time ranged from 6 months to 15 years. Thirty-six patients were treated with antiepileptic drugs and their seizures were easy to control. Four patients stayed seizure free without medication (all <2 years). Seizure stopped in 24 patients within 1 year of age, in 10 patients stopped during 12-24 months and in 2 patients stopped during 24-36 months. All cases had PRRT2 mutations, 7 cases of a complete PRRT2 deletion, 33 cases of PRRT2 heterozygous mutations consisted of 28 frameshift mutations and 5 missense mutations. Of these heterozygous mutations, 30 cases were hereditary mutations while 3 were de novo mutations. Nine family members harbored the same PRRT2 mutations without any symptom.
Conclusions
Benign infantile epilepsy with PRRT2 mutation is characterized by early onset of seizure mostly before 6 months, focal seizures with or without secondary generalization, a high incidence of a cluster of seizures, rapid resolution of seizure by antiepileptic drugs and cessation of seizure mostly before 2 years of age. Partial patients may develop paroxysmal kinesigenic dyskinesia increasing with age. Most PRRT2 gene mutations are heterozygous mutations, and a few are the overall deletion of PRRT2 gene.
10. Clinical and genetic characteristics of children with Leigh syndrome
Fang FANG ; Ying SHEN ; Danmin SHEN ; Zhimei LIU ; Changhong DING ; Wuchang ZHANG ; Suzhen SUN ; Junlan LYU ; Tongli HAN ; Xiaohui WANG ; Weihua ZHANG ; Xinying YANG ; Jiuwei LI ; Husheng WU
Chinese Journal of Pediatrics 2017;55(3):205-209
Objective:
To investigate the clinically and genetic characteristics of children with Leigh syndrome.
Method:
Patients with clinically diagnosed Leigh syndrome(LS)in the department of Neurology, Beijing Children′s Hospital from January 2013 to February 2016 underwent the mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) detecting with next generation sequencing (NGS) technology. The clinical data of gene confirmed cases were retrospectively collected and analyzed. The differences in the onset age, clinical manifestations, lactic acid level and MRI results between the mtDNA variation and nDNA variation were compared and analyzed.