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1.
J Neurol Sci ; 447: 120597, 2023 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-36965413

RESUMO

OBJECTIVE: In glucose transporter 1 deficiency syndrome (Glut1DS), cerebrospinal fluid glucose (CSFG) and CSFG to blood glucose ratio (CBGR) show significant differences among groups classified by phenotype or genotype. The purpose of this study was to investigate the association between these biochemical parameters and Glut1DS severity. METHODS: The medical records of 45 patients who visited Osaka University Hospital between March 2004 and December 2021 were retrospectively examined. Neurological status was determined using the developmental quotient (DQ), assessed using the Kyoto Scale of Psychological Development 2001, and the Scale for the Assessment and Rating of Ataxia (SARA). CSF parameters included CSFG, CBGR, and CSF lactate (CSFL). RESULTS: CSF was collected from 41 patients, and DQ and SARA were assessed in 24 and 27 patients, respectively. Simple regression analysis showed moderate associations between neurological status and biochemical parameters. CSFG resulted in a higher R2 than CBGR in these analyses. CSF parameters acquired during the first year of life were not comparable to those acquired later. CSFL was measured in 16 patients (DQ and SARA in 11 and 14 patients, respectively). Although simple regression analysis also showed moderate associations between neurological status and CSFG and CSFL, the multiple regression analysis for DQ and SARA resulted in strong associations through the use of a combination of CSFG and CSFL as explanatory variables. CONCLUSION: The severity of Glut1DS can be predicted from CSF parameters. Glucose and lactate are independent contributors to the developmental and neurological status in Glut1DS.


Assuntos
Glicemia , Glucose , Estudos Retrospectivos , Transportador de Glucose Tipo 1/genética , Glucose/líquido cefalorraquidiano , Ácido Láctico , Líquido Cefalorraquidiano
2.
Int Heart J ; 57(1): 112-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26673445

RESUMO

Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene which encodes dystrophin protein. Dystrophin defect affects cardiac muscle as well as skeletal muscle. Cardiac dysfunction is observed in all patients with DMD over 18 years of age, but there is no curative treatment for DMD cardiomyopathy. To establish novel experimental platforms which reproduce the cardiac phenotype of DMD patients, here we established iPS cell lines from T lymphocytes donated from two DMD patients, with a protocol using Sendai virus vectors. We successfully conducted the differentiation of the DMD patient-specific iPS cells into beating cardiomyocytes. DMD patient-specific iPS cells and iPS cell-derived cardiomyocytes would be a useful in vitro experimental system with which to investigate DMD cardiomyopathy.


Assuntos
Células-Tronco Pluripotentes Induzidas/fisiologia , Distrofia Muscular de Duchenne/metabolismo , Miócitos Cardíacos/citologia , Adolescente , Adulto , Diferenciação Celular , Células Cultivadas , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/patologia , Miócitos Cardíacos/metabolismo , RNA/genética , Reação em Cadeia da Polimerase em Tempo Real
3.
Brain Dev ; 37(7): 669-76, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25459970

RESUMO

BACKGROUND: More than 90% of spinal muscular atrophy (SMA) patients show homozygous deletion of SMN1 (survival motor neuron 1). They retain SMN2, a highly homologous gene to SMN1, which may partially compensate for deletion of SMN1. Although the promoter sequences of these two genes are almost identical, a GCC insertion polymorphism has been identified at c.-320_-321 in the SMN1 promoter. We have also found this insertion polymorphism in an SMN2 promoter in an SMA patient (Patient A) who has SMA type 2/3. PURPOSE: The aims of this study were to determine the frequency of the GCC insertion polymorphism in SMA patients, and to evaluate its effect on SMN transcription efficiency. PATIENTS AND METHODS: Fifty-one SMA patients, including Patient A, were involved in this study. SMN2 transcript levels in white blood cells were measured by real-time polymerase chain reaction. Screening of the GCC insertion polymorphism was performed using denaturing high-pressure liquid chromatography. The transcription efficiency of the promoter with the insertion mutation was evaluated using a reporter-gene assay. RESULTS: All SMA patients in this study were homozygous for SMN1 deletion. Patient A retained two copies of SMN2, and showed only a small amount of SMN2 transcript in white blood cells. We detected a GCC insertion polymorphism at c.-320_-321 only in Patient A, and not in 50 other SMA patients. The polymorphism had a slight but significant negative effect on transcription efficiency. DISCUSSION AND CONCLUSION: Patient A was judged to be an exceptional case of SMA, because the GCC insertion polymorphism rarely exists in SMN1-deleted SMA patients. The GCC insertion polymorphism did not enhance the transcriptional efficiency of SMN2. Thus, this GCC insertion polymorphism in the SMN2 promoter may not be associated with the milder phenotype of the patient. Patient A suggests that there are other unknown factors modifying the clinical phenotype of SMA.


Assuntos
Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/genética , Mutação , Regiões Promotoras Genéticas , Proteína 1 de Sobrevivência do Neurônio Motor/genética , Adolescente , Adulto , Sequência de Bases , Criança , Pré-Escolar , Feminino , Deleção de Genes , Dosagem de Genes , Humanos , Lactente , Masculino , Dados de Sequência Molecular , Fenótipo , Polimorfismo Genético , Proteína 2 de Sobrevivência do Neurônio Motor/genética , Adulto Jovem
4.
Brain Dev ; 37(2): 191-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24787271

RESUMO

OBJECTIVE: To determine the prognostic factors for encephalopathy with bright tree appearance (BTA) in the acute phase through retrospective case evaluation. METHODS: We recruited 10 children with encephalopathy who presented with BTA and classified them into 2 groups. Six patients with evident regression and severe psychomotor developmental delay after encephalopathy were included in the severe group, while the remaining 4 patients with mild mental retardation were included in the mild group. We retrospectively analyzed their clinical symptoms, laboratory data, and magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) findings. RESULTS: Patients in the severe group developed subsequent complications such as epilepsy and severe motor impairment. Univariate analysis revealed that higher maximum lactate dehydrogenase (LDH) levels (p=0.055) were a weak predictor of poor outcome. Maximum creatinine levels were significantly higher (p<0.05) and minimal platelet counts were significantly lower (p<0.05) in the severe group than in the mild group. Acute renal failure was not observed in any patient throughout the study. MRS of the BTA lesion during the BTA period showed elevated lactate levels in 5 children in the severe group and 1 child in the mild group. MRI performed during the chronic phase revealed severe brain atrophy in all patients in the severe group. CONCLUSIONS: Higher creatinine and LDH levels and lower platelet counts in the acute phase correlated with poor prognosis. Increased lactate levels in the BTA lesion during the BTA period on MRS may predict severe physical and mental disability.


Assuntos
Encefalopatias/sangue , Encefalopatias/diagnóstico , Encéfalo/metabolismo , Encéfalo/patologia , Doença Aguda , Ansiolíticos/uso terapêutico , Encefalopatias/complicações , Criança , Pré-Escolar , Creatinina/sangue , Diazepam/uso terapêutico , Epilepsia/complicações , Humanos , Lactente , L-Lactato Desidrogenase/sangue , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Midazolam/uso terapêutico , Estudos Retrospectivos
5.
Seizure ; 23(7): 521-6, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24768270

RESUMO

PURPOSE: Epileptic spasms sometimes begin after the first year of life, and such seizures are recognized as late-onset spasms (LOS). The prognosis of LOS is poor, and a treatment strategy has not been established. This study aimed to assess the short- and long-term effects of adrenocorticotropic hormone (ACTH) therapy for LOS. METHODS: We investigated the rate of LOS in 22 patients (14 boys and 8 girls) treated with ACTH therapy. The age at onset of LOS and at the start of ACTH therapy ranged from 12 to 94 months (median, 31.6 ± 22.1 months) and from 12.5 to 116 months (median, 37.5 ± 23.7 months), respectively. We investigated the response rate of LOS treated with ACTH therapy, and compared the clinical features between responders (short-term) and nonresponders. RESULTS: Nine (41%) of the 22 patients showed cessation of epileptic spasms within 3 months. The epileptic spasms ceased in four of these nine patients for more than 1 year. The age at onset of LOS was significantly associated with short-term seizure cessation (p<0.05). Patients who achieved short-term cessation of seizures received ACTH therapy within 6 months from the onset of LOS. CONCLUSION: ACTH therapy is a potentially effective treatment when started within 6 months from the onset of LOS. A younger age at onset of LOS is associated with a favorable outcome.


Assuntos
Hormônio Adrenocorticotrópico/uso terapêutico , Hormônios/uso terapêutico , Espasmos Infantis/tratamento farmacológico , Fatores Etários , Idade de Início , Criança , Pré-Escolar , Eletroencefalografia , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Resultado do Tratamento
6.
Neurol Med Chir (Tokyo) ; 53(11): 814-20, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24140769

RESUMO

Children with unilobar or multilobar pathology issuing in refractory epilepsy are potential candidates for surgical treatment. Extensive surgery results in good seizure control, but it also increases the risk of neurological deficits as well as motor and mental problems. We reviewed the cases of 19 children with refractory epilepsy treated surgically at Osaka University Hospital. Four of the 19 patients underwent temporal disconnection, 2 underwent occipital lobectomy, 4 underwent temporoparietooccipital disconnection, 6 underwent functional hemispherotomy, and 3 underwent corpus callosotomy. A good surgical outcome, i.e., Engel's class I or II, was achieved in 12 (63%) of the 19 patients. Excellent surgical outcomes and satisfactory motor and mental development were achieved in 4 patients who underwent temporoparietooccipital disconnection. The outcomes of functional hemispherectomy were also satisfactory. The outcomes of temporal disconnection and corpus callosotomy were poor in comparison to outcomes of the other procedures. We believe that better surgical outcomes would have been achieved with temporoparietooccipital disconnection in some cases treated by temporal disconnection or occipital resection. Adequate extensive surgical procedures should be considered for refractory childhood epilepsy arising from unilobar or multilobar pathology.


Assuntos
Epilepsia/cirurgia , Procedimentos Neurocirúrgicos/métodos , Adolescente , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Dano Encefálico Crônico/etiologia , Dano Encefálico Crônico/prevenção & controle , Córtex Cerebral/cirurgia , Criança , Pré-Escolar , Corpo Caloso/cirurgia , Resistência a Medicamentos , Epilepsia/tratamento farmacológico , Feminino , Hemisferectomia/efeitos adversos , Humanos , Lactente , Masculino , Malformações do Desenvolvimento Cortical/complicações , Malformações do Desenvolvimento Cortical/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Resultado do Tratamento
7.
No To Hattatsu ; 45(1): 49-52, 2013 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-23593746

RESUMO

We report a case of a 15-year-old girl with relapsing-remitting multiple sclerosis (MS) who received cyclophosphamide pulse therapy. At the age of 5 years, she displayed symptoms such as headache and unconsciousness after varicella infection as the first episode of MS. She had been treated with methylprednisolone pulse therapy, intravenous immunoglobulin, interferon-beta1b, and azathioprine. However, she had relapsed 12 times by the age of 15 years. At this time, she showed weakness and severe paralysis of her left leg, and even 1 month after methylprednisolone pulse therapy, she still had gait impairment and showed gadolinium-enhanced lesion on brain magnetic resonance imaging. We then started cyclophosphamide pulse therapy (600 mg/m2) once a month for 12 months combined with interferon-beta1a. She had no serious side effects and she could walk again after 4 months on cyclophosphamide treatment. She has been free from relapse for 2 years and 8 months until the present time. Although only a few studies have indicated the efficacy of cyclophosphamide pulse therapy for childhood MS, we consider careful use of cyclophosphamide could be one of the options for refractory childhood MS.


Assuntos
Ciclofosfamida/uso terapêutico , Imunossupressores/uso terapêutico , Interferon beta/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adolescente , Quimioterapia Combinada/métodos , Feminino , Humanos , Interferon beta-1a , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Prevenção Secundária , Resultado do Tratamento
8.
Gene ; 515(1): 173-80, 2013 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-23266643

RESUMO

BACKGROUND: Left ventricular noncompaction (LVNC) is a cardiomyopathy characterized by a prominent trabecular meshwork and deep intertrabecular recesses, and is thought to be due to an arrest of normal endomyocardial morphogenesis. However, the genes contributing to this process remain poorly understood. 14-3-3ε, encoded by YWHAE, is an adapter protein belonging to the 14-3-3 protein family which plays important roles in neuronal development and is involved in Miller-Dieker syndrome. We recently showed that mice lacking this gene develop LVNC. Therefore, we hypothesized that variants in YWHAE may contribute to the pathophysiology of LVNC in humans. METHODS AND RESULTS: In 77 Japanese patients with LVNC, including the probands of 29 families, mutation analysis of YWHAE by direct DNA sequencing identified 7 novel variants. One of them, c.-458G>T, in the YWHAE promoter, was identified in a familial patient with LVNC and hypoplasia of the corpus callosum. The -458G>T variant is located within a regulatory CCAAT/enhancer binding protein (C/EBP) response element of the YWHAE promoter, and it reduced promoter activity by approximately 50%. Increased binding of an inhibitory C/EBPß isoform was implicated in decreasing YWHAE promoter activity. Interestingly, we had previously shown that C/EBPß is a key regulator of YWHAE. CONCLUSIONS: These data suggest that the -458G>T YWHAE variant contributes to the abnormal myocardial morphogenesis characteristic of LVNC as well as abnormal brain development, and implicate YWHAE as a novel candidate gene in pediatric cardiomyopathies.


Assuntos
Proteínas 14-3-3/genética , Agenesia do Corpo Caloso/genética , Povo Asiático/genética , Corpo Caloso/metabolismo , Variação Genética , Miocárdio Ventricular não Compactado Isolado/genética , Sequência de Bases , Criança , Pré-Escolar , Éxons , Evolução Fatal , Feminino , Frequência do Gene , Humanos , Lactente , Recém-Nascido , Japão , Masculino , Dados de Sequência Molecular , Mutação , Linhagem , Regiões Promotoras Genéticas
9.
J Hum Genet ; 58(1): 33-9, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23223008

RESUMO

Duchenne muscular dystrophy (DMD) is the most common inherited muscular disease and is characterized by progressive muscle wasting. DMD is caused by mutations in the dystrophin gene on Xp21.2. One-third of DMD cases are complicated by mental retardation, but the pathogenesis of this is unknown. We have identified an intrachromosomal inversion, inv(X)(p21.2;q28) in a DMD patient with mental retardation. We hypothesized that a gene responsible for the mental retardation in this patient would be disrupted by the inversion. We localized the inversion break point by analysis of dystrophin complementary DNA (cDNA) and fluorescence in situ hybridization. We used 5' and 3' rapid amplification of cDNA ends to extend the known transcripts, and reverse transcription-PCR to analyze tissue-specific expression. The patient's dystrophin cDNA was separated into two fragments between exons 18 and 19. Exon 19 was dislocated to the long arm of the X-chromosome. We identified a novel 109-bp sequence transcribed upstream of exon 19, and a 576-bp sequence including a poly(A) tract transcribed downstream of exon 18. Combining the two novel sequences, we identified a novel gene, named KUCG1, which comprises three exons spanning 50 kb on Xq28. The 685-bp transcript has no open-reading frame, classifying it as a long non-coding RNA. KUCG1 mRNA was identified in brain. We cloned a novel long non-coding gene from a chromosomal break point. It was supposed that this gene may have a role in causing mental retardation in the index case.


Assuntos
Inversão Cromossômica , Cromossomos Humanos X/genética , Distrofina/genética , Deficiência Intelectual/genética , Distrofia Muscular de Duchenne/genética , RNA Longo não Codificante/metabolismo , Encéfalo/metabolismo , Pré-Escolar , Quebra Cromossômica , DNA Complementar/genética , Éxons/genética , Humanos , Hibridização in Situ Fluorescente , Masculino , Distrofia Muscular de Duchenne/complicações , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
10.
Am J Med Genet A ; 161A(1): 203-7, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23239615

RESUMO

We reported on a male patient with rare leukoencephalopathy and skeletal abnormalities. The condition was first noticed as a developmental delay, nystagmus and ataxia at 1 year of age. At 4 years of age, he was diagnosed as hypomyelination with skeletal abnormalities from clinical features, brain magnetic resonance imaging (MRI) and skeletal X-rays. His brain MRI revealed diffuse hypomyelination. These findings suggested the classical type of Pelizaeus-Merzbacher disease (PMD) caused by proteolipid protein (PLP)-1 gene or Pelizaeus-Merzbacher-like disease (PMLD). However, we found neither mutation nor duplication of PLP-1. The patient had severe growth retardation and general skeletal dysplasia compatible with spondylo-epi-metaphyseal dysplasia; however the mutation of discoidin domain receptor (DDR) 2 gene was absent. The co-morbidity of hypomyelination with skeletal abnormalities is rare. We performed array CGH and no causal copy number variation was recognized. Alternatively, this condition may have been caused by a mutation of the gene encoding a molecule that functions in both cerebral myelination and skeletal development.


Assuntos
Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/genética , Doenças Mitocondriais/genética , Osteocondrodisplasias/genética , Transtornos Psicomotores/genética , Sistemas de Transporte de Aminoácidos Acídicos/deficiência , Sistemas de Transporte de Aminoácidos Acídicos/genética , Antiporters/deficiência , Antiporters/genética , Tronco Encefálico/anormalidades , Tronco Encefálico/patologia , Criança , Pré-Escolar , Variações do Número de Cópias de DNA , Receptores com Domínio Discoidina , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/diagnóstico , Humanos , Processamento de Imagem Assistida por Computador , Lactente , Imageamento por Ressonância Magnética , Masculino , Análise em Microsséries , Doenças Mitocondriais/diagnóstico , Mutação , Proteína Proteolipídica de Mielina/genética , Osteocondrodisplasias/diagnóstico , Doença de Pelizaeus-Merzbacher/diagnóstico , Doença de Pelizaeus-Merzbacher/genética , Transtornos Psicomotores/diagnóstico , Receptores Proteína Tirosina Quinases/genética , Receptores Mitogênicos/genética
11.
Epilepsy Res ; 102(1-2): 60-70, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22647843

RESUMO

OBJECTIVES: High-frequency oscillations (HFOs) on intracranial electroencephalography (EEG) recordings have been reported to be useful to identify the epileptogenic zone in intractable epilepsy. We investigated whether the ictal HFOs on scalp EEG seen during spasms contributed to identification of the epileptogenic zone in symptomatic West syndrome (S-WS). METHODS: In S-WS, ictal scalp EEGs were recorded during a series of spasms. The HFOs associated with spasms were visualized in the temporally expanded EEG traces and subjected to time-frequency analysis. The results on the distribution of HFOs were compared with that of cortical lesions indicated by neuroimaging. RESULTS: In the 4 children examined, HFOs at 80-150 Hz preceded the clinical onsets of spasms. The maximum augmentation of these HFOs was larger than that of HFOs at 20-70 Hz. The regions of the maximum augmentation of HFOs at 80-150 Hz were identical to the lesions detected by neuroimaging. Two patients who underwent dissection of the area including the area with HFOs resulted in Engel class I. CONCLUSION: Ictal HFOs of spasms on scalp EEG showed a strong association with neuroimaging abnormalities presumed to be the epileptogenic zone in S-WS. Ictal HFOs can thus be a useful marker for exploring lesions for epilepsy surgery.


Assuntos
Mapeamento Encefálico/métodos , Eletroencefalografia/métodos , Cuidados Pré-Operatórios/métodos , Espasmos Infantis/diagnóstico , Espasmos Infantis/fisiopatologia , Idade de Início , Síndrome de Aicardi/diagnóstico , Síndrome de Aicardi/fisiopatologia , Síndrome de Aicardi/cirurgia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Malformações do Desenvolvimento Cortical/diagnóstico , Malformações do Desenvolvimento Cortical/fisiopatologia , Malformações do Desenvolvimento Cortical/cirurgia , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Espasmos Infantis/cirurgia , Tomografia Computadorizada de Emissão de Fóton Único
12.
Brain Dev ; 34(9): 731-8, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22336751

RESUMO

It has been hypothesized that early seizure control may prevent children with intractable epileptic spasms (ES) from developmental regression and may contribute to better developmental outcome. The effectiveness of surgery for ES has been reported. We investigated long-term post-operative outcomes of seizure control and development in patients with symptomatic West syndrome (S-WS) who underwent epilepsy surgery. Six children who underwent surgical intervention for intractable ES were retrospectively investigated. Cortical malformations were observed on pre-operative MRI in all patients, with hemispheric or multilobar involvement in four children and focal lesions in two. Following surgery, we measured motor function, developmental age (DA), language skills, and sociopsychological function for up to 7years (mean, 4.9years). Post-operative seizure outcome was Engel Class I (n=4) or III (n=2). Motor function and DA was increased following surgery in six and five patients, respectively. Two patients started to speak in sentences following focal resection. Autistic features were noted in four of the five examined patients post-operatively. None of the patients showed developmental regression following surgery. Epilepsy surgery for S-WS with ES may result in good seizure control and improvement in motor development. Improvement in cognitive function was modest in this small cohort of children and autistic features were noted post-operatively in a substantial proportion of the children. While seizure control can be obtained by epilepsy surgery, early intervention for sociopsychological comorbidities may be warranted in children with S-WS.


Assuntos
Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias/etiologia , Espasmos Infantis/etiologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Eletroencefalografia , Epilepsia/cirurgia , Fluordesoxiglucose F18 , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Espasmos Infantis/diagnóstico , Tomografia Computadorizada de Emissão de Fóton Único
13.
No To Hattatsu ; 44(1): 13-8, 2012 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-22352024

RESUMO

Botulinum toxin A (BTX-A) therapy has been approved as a first-line therapy for spastic torticollis. However it has been suggested as that its use in patients with respiratory distress should be decided cautiously. We treated 5 patients with abnormal posture, cervical hypertonia and obstructive respiratory distress by BTX-A, and analyzed its efficacy for respiratory distress by their Tsui score and respiratory status after BTX-A therapy. All 5 patients clinically had some degree of dysphagia before BTX-A therapy. Cervical hypertonia and induced abnormal posture were improved in all patients. The youngest patient could control muscle tone after only 2 doses of BTX-A and subsequently maintained a good condition without additional BTX-A. BTX-A therapy can decrease torsion and hyperextension of the upper respiratory tract by reducing cervical hypertonia. Consequently, it may improve respiratory status. On the other hand, mild dysphagia and excessive salivation was noted in one patient for each symptom. It is safe to avoid BTX-A invasion to the anterior muscle of neck and rapid changes in the swallowing pattern.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Hipertonia Muscular/complicações , Hipertonia Muscular/tratamento farmacológico , Músculos do Pescoço/fisiopatologia , Insuficiência Respiratória/tratamento farmacológico , Insuficiência Respiratória/etiologia , Adolescente , Adulto , Criança , Feminino , Humanos , Lactente , Masculino , Resultado do Tratamento
14.
Brain Dev ; 34(2): 156-62, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21356581

RESUMO

Giant axonal neuropathy (GAN) is a rare autosomal recessive disorder that affects both the peripheral nerves and central nervous system. Since the discovery in 2000 of the gigaxonin gene on chromosome 16q24.1 to be causative, more than 40 GAN mutations have been reported from different racial backgrounds. We report the clinicogenetic findings of a 24-year-old Japanese man with GAN. He had consanguineous parents and showed the phenotype of classical severe GAN. We found a novel homozygous nonsense mutation (p.R162X) in the GAN gene. This is the first genetically-determined Japanese case of GAN, with a follow-up period of more than 15 years. In addition, this mutation is novel. We also reviewed previous reports of GAN to see whether there is any genotype-phenotype correlation.


Assuntos
Proteínas do Citoesqueleto/genética , Neuropatia Axonal Gigante/genética , Neuropatia Axonal Gigante/patologia , Mutação/genética , Pré-Escolar , Análise Mutacional de DNA , Saúde da Família , Humanos , Japão , Imageamento por Ressonância Magnética , Masculino , Tomografia Computadorizada por Raios X
15.
J Hum Genet ; 56(12): 846-51, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22011817

RESUMO

Glucose transporter 1 deficiency syndrome (Glut1-DS) is a congenital metabolic disorder characterized by refractory seizures with early infantile onset, developmental delay, movement disorders and acquired microcephaly. Glut1-DS is caused by heterozygous abnormalities of the SLC2A1 (Glut1) gene, whose product acts to transport glucose into the brain across the blood-brain barrier. We analyzed the SLC2A1 gene in 12 Japanese Glut1-DS patients who were diagnosed by characteristic clinical symptoms and hypoglycorrhachia as follows: all patients had infantile-onset seizures and mild to severe developmental delay, and ataxia was detected in 11 patients. For the 12 patients, we identified seven different mutations (three missense, one nonsense, two frameshift and one splice-site) in exons and exon-intron boundaries of the SLC2A1 gene by direct sequencing, of which six were novel mutations. Of the remaining five patients who had no point mutations and underwent investigation by multiplex ligation-dependent probe amplification, a complex abnormality with deletion and duplication was identified in one patient: this is the first case of such recombination of the SLC2A1 gene. Changes in regulatory sequences in the promoter region or genes other than SLC2A1 might be responsible for onset of Glut1-DS in the other four patients (33%) without SLC2A1 mutation.


Assuntos
Transportador de Glucose Tipo 1/deficiência , Transportador de Glucose Tipo 1/genética , Adolescente , Povo Asiático/genética , Criança , Pré-Escolar , Análise Mutacional de DNA , Éxons , Feminino , Humanos , Japão , Masculino , Linhagem , Síndrome
17.
Allergol Int ; 59(4): 425-8, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20962570

RESUMO

BACKGROUND: Juvenile dermatomyositis is potentially life threatening rare autoimmune illness that mainly affects muscle and skin. Cutaneous features are useful in establishing the diagnosis of this disease. CASE SUMMARY: We report an 8-year-old male juvenile dermatomyositis who presented epidermal nevus like-lesions on the back of the right thigh. Characteristic cutaneous changes such as Gottron's papules of the hand, heliotrope rash of the eyelids, and poikiloderma-like lesions on the back were observed. Diagnosis of juvenile dermatomyositis was made by positive muscle biopsy and magnetic resonance imaging findings and typical cutaneous manifestations. However, epidermal nevus-like skin lesions, an acquired inflammatory dermatosis that follows Blaschko lines, seen in this case have been rarely reported in the literatures. DISCUSSION: We would like to report this case and discuss about the significance and pathogenesis of this rare cutaneous manifestation like Blaschkitis in juvenile dermatomyositis.


Assuntos
Tono Muscular/imunologia , Músculo Esquelético/patologia , Pele/patologia , Biópsia , Criança , Pré-Escolar , Dermatomiosite/diagnóstico , Dermatomiosite/tratamento farmacológico , Dermatomiosite/patologia , Dermatomiosite/fisiopatologia , Eritema , Humanos , Imunoglobulina E/sangue , Inflamação , Ceratodermia Palmar e Plantar , Masculino , Músculo Esquelético/imunologia , Nevo Sebáceo de Jadassohn , Prednisolona/uso terapêutico
18.
No To Hattatsu ; 41(5): 349-52, 2009 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-19764454

RESUMO

A 15-year-old girl had no REM sleep presumably due to a pontine cavernous hemangioma was reported. Her brain MRI revealed a cavernous hemangioma extending from the dorsal pontine to the medulla. She manifested truncal ataxia, facial nerve palsy, and ocular motor apraxia. She could not sleep in the supine position due to the sleep apnea accompanied with loud snoring. Overnight polysomnography (PSG) was performed for detection of obstructive sleep apnea syndrome (OSAS). In addition to severe OSAS and Cheyne-Stokes-like respiration at wake after sleep onset, her 1st PSG study revealed no periods with rapid eye movement, EEG characteristic of REM sleep, atonia and variation on respiratory and heart rate. Even after effective therapy for OSAS with non-invasive positive airway pressure ventilation (NPPV), her 2nd PSG also failed to show stage REM. These findings suggest that this pontine cavernous hemangioma disturbed her REM-on system. This is the first report of an individual with long-term loss of REM sleep and a valuable case for the understanding of anatomical structures of the REM-on system and the role of REM in memory consolidation.


Assuntos
Neoplasias do Tronco Encefálico/complicações , Hemangioma Cavernoso do Sistema Nervoso Central/complicações , Privação do Sono/etiologia , Adolescente , Neoplasias do Tronco Encefálico/diagnóstico , Respiração de Cheyne-Stokes/etiologia , Feminino , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico , Humanos , Imageamento por Ressonância Magnética , Obesidade/complicações , Polissonografia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/etiologia , Privação do Sono/diagnóstico
19.
Mol Genet Metab ; 98(3): 255-63, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19556155

RESUMO

The efficacy of hematopoietic stem cell transplantation (HSCT) for Hunter disease (deficiency of iduronate-2-sulfatase, IDS) remains unclear. We treated a 6-year-old male suffering from a severe type of Hunter disease with cord blood stem cell transplantation (CBSCT); however, he died at 10 months post-therapy due to a laryngeal post-transplantation lymphoproliferative disorder. During the follow-up period after CBSCT, his hyperactivity, estimated mental age, and brain MR findings had not improved. We assessed the efficacy of CBSCT by biochemical and pathological analyses of the autopsied tissues. There were many distended cells with accumulated substrate in the brain, but not in the liver. IDS enzyme activity in the cerebrum remained very low, although that in the liver reached about 40% of the normal control level. However, a variable number of tandem repeats analyses demonstrated a weak donor-derived band not only in the liver but also in the cerebrum. Furthermore, IDS-immunoreactivity in the liver was recognized broadly not only in Kupffer cells but also in hepatocytes. On the other hand, IDS-immunoreactivity was recognized exclusively in CD68-positive microglia/monocytes in the patient's brain; whereas that in the normal brain was also detected in neurons and oligodendrocytes. These donor-derived IDS-positive cells were predominantly localized in perivascular spaces and some of them were evidently present in the brain parenchyma. The efficacy of CBSCT was judged to be insufficient for the brain at 10 months post-therapy. However, the pathological detection of donor-derived cells in the brain parenchyma suggests the potential of HSCT for treatment of neurological symptoms in Hunter disease. This is the first neuropathological report documenting the distribution of donor-derived cells in the brain after CBSCT into a Hunter disease patient.


Assuntos
Encéfalo/patologia , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Mucopolissacaridose II/patologia , Mucopolissacaridose II/terapia , Encéfalo/metabolismo , Criança , Transplante de Células-Tronco Hematopoéticas , Humanos , Imageamento por Ressonância Magnética , Masculino , Doadores de Tecidos
20.
Brain Dev ; 31(3): 234-9, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18495398

RESUMO

OBJECTIVES: To clarify the feature of sleep disordered breathing (SDB) associated with childhood-onset acid maltase deficiency (AMD): the progressive nature of SDB and the stage of AMD. STUDY DESIGN: We retrospectively studied 4 patients with childhood-onset AMD by analyzing the results of neurological examinations for muscle wasting and muscle strength and the data on venous gas and from a pulmonary function test and nocturnal polysomnography (PSG). RESULTS: Three out of the 4 patients showed muscular symptoms including myalgia, lordoscoliosis, muscle wasting and muscle weakness. They also complained of sleep-related symptoms such as tiredness in the morning and daytime sleepiness. All of them showed SDB by PSG, even in a patient in the earliest stage who exhibited no signs or symptoms of muscle weakness. In 3 patients, noninvasive intermittent positive pressure ventilation during sleep was introduced; and thereafter sleep-related symptoms were resolved and no lower respiratory infection reoccurred. Although their quality of life was improved, no improvement of respiratory function was shown by spirometry over a 2-year follow-up period. CONCLUSIONS: SDB seems to be common in childhood-onset AMD, which is not always accompanied by daytime muscular symptoms, especially in mild patients. PSG should be utilized for detecting SDB, which could be one of the earliest signs of respiratory muscle involvement in childhood-onset AMD.


Assuntos
Doença de Depósito de Glicogênio Tipo II/fisiopatologia , Síndromes da Apneia do Sono/fisiopatologia , Síndromes da Apneia do Sono/terapia , Adolescente , Gasometria , Criança , Feminino , Humanos , Masculino , Força Muscular , Debilidade Muscular , Polissonografia , Respiração com Pressão Positiva , Qualidade de Vida , Respiração , Transtornos Respiratórios/fisiopatologia , Transtornos Respiratórios/terapia , Testes de Função Respiratória , Estudos Retrospectivos , Sono/fisiologia
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