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1.
Mol Ther Nucleic Acids ; 20: 687-698, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32388194

RESUMO

Here, we report on validating a mitochondrial gene therapy by delivering nucleic acids to mitochondria of diseased cells by a MITO-Porter, a liposome-based carrier for mitochondrial delivery. We used cells derived from a patient with a mitochondrial disease with a G625A heteroplasmic mutation in the tRNAPhe of the mitochondrial DNA (mtDNA). It has been reported that some mitochondrial gene diseases are caused by heteroplasmic mutations, in which both mutated and wild-type (WT) genes are present, and the accumulation of pathological mutations leads to serious, intractable, multi-organ diseases. Therefore, the decrease of the mutated gene rate is considered to be a useful gene therapy strategy. To accomplish this, wild-type mitochondrial pre-tRNAPhe (pre-WT-tRNAPhe), prepared by in vitro transcription, was encapsulated in the MITO-Porter. The pre-WT-tRNAPhe encapsulated in the MITO-Porter was transfected into diseased mitochondrial cells, and the resulting mutant levels were examined by an amplification refractory mutation system (ARMS)-quantitative PCR. The mutation rate of tRNAPhe was decreased, and this therapeutic effect was sustained even on the 8th day after transfection. Furthermore, mitochondrial respiratory activity of the disease cells was increased after the transfection of therapeutic pre-WT-tRNAPhe. These results support the conclusion that the mitochondrial delivery of therapeutic nucleic acids represents a viable strategy for mitochondrial gene therapy.

2.
Mol Genet Metab Rep ; 25: 100684, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34589414

RESUMO

Hypertension is a rare complication of Leigh Syndrome (LS), but prognosis of patients with hypertension is poor and its presence is indicative of the terminal stage of the disease. Herein, we report a four-year-old girl case diagnosed with LS at 15 months of age who subsequently developed severe hypertension and respiratory failure. Physical examination and laboratory findings did not indicate a secondary cause of hypertension. Her respiratory failure was treated with non-invasive ventilation and hypertension controlled with enalapril, furosemide and spironolactone. To our knowledge, this is the first case of a patient with LS recovering from severe hypertension.

3.
EBioMedicine ; 30: 86-93, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29506874

RESUMO

Mutations in the m.13094T>C MT-ND5 gene have been previously described in three cases of Leigh Syndrome (LS). In this retrospective, international cohort study we identified 20 clinically affected individuals (13 families) and four asymptomatic carriers. Ten patients were deceased at the time of analysis (median age of death was 10years (range: 5·4months-37years, IQR=17·9years). Nine patients manifested with LS, one with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), and one with Leber hereditary optic neuropathy. The remaining nine patients presented with either overlapping syndromes or isolated neurological symptoms. Mitochondrial respiratory chain activity analysis was normal in five out of ten muscle biopsies. We confirmed maternal inheritance in six families, and demonstrated marked variability in tissue segregation, and phenotypic expression at relatively low blood mutant loads. Neuropathological studies of two patients manifesting with LS/MELAS showed prominent capillary proliferation, microvacuolation and severe neuronal cell loss in the brainstem and cerebellum, with conspicuous absence of basal ganglia involvement. These findings suggest that whole mtDNA genome sequencing should be considered in patients with suspected mitochondrial disease presenting with complex neurological manifestations, which would identify over 300 known pathogenic variants including the m.13094T>C.


Assuntos
Encéfalo/patologia , Complexo I de Transporte de Elétrons/genética , Proteínas Mitocondriais/genética , Mutação/genética , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Criança , Estudos de Coortes , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Síndrome , Adulto Jovem
4.
Int J Adolesc Med Health ; 29(2)2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26536575

RESUMO

BACKGROUND: Few studies have investigated interactive health literacy (IHL)'s relationship with adolescents' smoking-related behavior. This study investigated IHL's association with adolescents' susceptibility to future smoking. MATERIALS AND METHODS: We conducted a school-based cross-sectional study of Japanese students enrolled in public junior high school, grades 7-9 (n=1937), who completed a self-report questionnaire. Variables were grade, gender, media exposure [television (TV), internet, and magazines], IHL (interest in learning about health, understanding what they hear about health, trying to follow what is taught about health), and susceptibility to future smoking. RESULTS: Significant findings were: [1] media exposure was positively associated with adolescents' susceptibility to future smoking (TV: p<0.01, internet: p<0.01, magazines: p<0.01); [2] IHL was negatively associated with adolescents' susceptibility to future smoking (interest in learning about health: p<0.001; understanding what they hear about health: p<0.05; trying to follow what is taught about health: p<0.001). IHL's influence on susceptibility to future smoking was found to be marginally stronger than that of media exposure. CONCLUSION: School health-education programs that promote adolescents' IHL may effectively reduce adolescents' susceptibility to future smoking.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Letramento em Saúde/métodos , Meios de Comunicação de Massa , Fumar/psicologia , Adolescente , Comportamento do Adolescente , Estudos Transversais , Feminino , Humanos , Internet , Masculino , Análise de Regressão , Instituições Acadêmicas , Prevenção do Hábito de Fumar , Estudantes , Inquéritos e Questionários
5.
No To Hattatsu ; 46(1): 39-43, 2014 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-24620430

RESUMO

MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) is the most representative subtype of mitochondrial diseases. Administration of L-arginine (L-Arg) or a precursor of nitric oxide (NO) has been proposed as a promising medication for MELAS because one of the pathophysiological mechanisms is supposedly a decreased capacity for NO-dependent vasodilation. We experienced a girl with MELAS and frequent stroke-like episodes who was treated with L-Arg infusion. We evaluated the efficacy of L-Arg infusion therapy based on whether her headache and nausea were disappeared and neurological symptoms were improved within 24 hours of L-Arg administration. L-Arg infusions were effective in all four episodes when the treatment was started within 4 hours of the onset of stroke-like episodes. On the other hand, the infusion was effective in only one out of five episodes when the medication was delayed by more than 4 hours after the onset. Furthermore, the early administration of L-Arg resulted in better outcomes regarding new lesions determined by brain MRI. Our data suggest that L-Arg infusion may be most effective when it is started within 4 hours of the onset of neurological symptoms in the acute phase of MELAS. The study of a large number of episodes in many patients will be needed to determine the critical time point of L-Arg administration after the onset of the acute phase of MELAS.


Assuntos
Arginina/uso terapêutico , Síndrome MELAS/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Arginina/administração & dosagem , Criança , Humanos , Infusões Intravenosas , Síndrome MELAS/diagnóstico , Imageamento por Ressonância Magnética/métodos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Fatores de Tempo , Resultado do Tratamento
6.
No To Hattatsu ; 45(6): 452-6, 2013 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-24313005

RESUMO

Severe infantile form of nemaline myopathy is clinically characterized by marked muscle hypotonia and weakness with respiratory and feeding difficulties since infancy. Recently, mutations in the skeletal muscle alpha-actine gene (ACTA1) have been identified in many patients with the nemaline myopathy. We experienced two cases of severe infantile form of nemaline myopathy with ACTA1 mutation (missence heterozygous mutation;c.553C>T, p.R185C) in siblings presenting with different clinical symptoms and courses. The elder brother was a typical "floppy infant" at birth. Because he could not suck and swallow at all, he was fed completely through a nasogastric tube. At 2 months of age, he developed respiratory insufficiency and was placed on a respirator all day. He was diagnosed with having nemaline myopathy from his muscle biopsy, which revealed marked variation in muscle fiber size with large numbers of nemaline bodies on Gomori-trichrome stain. In contrast, the younger brother presented with mild muscular hypotonia and feeding difficulty during the neonatal stage;therefore, he was partly fed through a nasogastric tube. At 2 months of age, he was admitted to our hospital because of respiratory distress, and he required nasal continuous positive airway pressure with oxygen followed by noninvasive positive pressure ventilation intermittently, mainly at night. He was followed at his home by parents with no serious problems;however he unexpectedly died at the age of 15 months. Although most cases of severe infantile form of nemaline myopathy caused by ACTA1 mutations are sporadic and have no family history, we emphasize that clinical symptoms are variable in siblings with the same mutation.


Assuntos
Músculo Esquelético/patologia , Doenças Musculares/genética , Mutação/genética , Miopatias da Nemalina/genética , Actinas/genética , Humanos , Recém-Nascido , Masculino , Doenças Musculares/patologia , Miopatias da Nemalina/patologia , Irmãos
7.
ISRN Obstet Gynecol ; 2013: 709616, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24167731

RESUMO

Objective. We investigated the effects of the centralization of obstetricians and obstetric care facilities on the perinatal mortality rate in Japan. Methods. We used the Gini coefficient as an index to represent the centralization of obstetricians and obstetric care facilities. The Gini coefficients were calculated for the number of obstetricians and obstetric care facilities of 47 prefectures using secondary medical care zones as units. To measure the effects of the centralization of obstetricians and obstetric care facilities on the outcomes (perinatal mortality rates), we performed multiple regression analysis using the perinatal mortality rate as the dependent variable. Results. Obstetric care facilities were more evenly distributed than obstetricians. The perinatal mortality rate was found to be significantly negatively correlated with the number of obstetricians per capita and the Gini coefficient of obstetric care facilities. The latter had a slightly stronger effect on the perinatal mortality rate. Conclusion. The centralization of obstetric care facilities can improve the perinatal mortality rate, even when increasing the number of obstetricians is difficult.

8.
Neurogenetics ; 13(4): 327-32, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22847149

RESUMO

Whole-exome sequencing of two affected sibs and their mother who showed a unique quadriceps-dominant form of neurogenic muscular atrophy disclosed a heterozygous DYNC1H1 mutation [p.H306R (c.917A>G)]. The identical mutation was recently reported in a pedigree with the axonal form of Charcot-Marie-Tooth disease. Three other missense mutations in DYNC1H1 were also identified in families with dominant spinal muscular atrophy with lower extremity predominance. Their clinical features were consistent with those of our family. Our study has demonstrated that the same DYNC1H1 mutation could cause spinal muscular atrophy as well as distal neuropathy, indicating pleotropic effects of the mutation.


Assuntos
Dineínas do Citoplasma/genética , Genes Dominantes , Deformidades Congênitas das Extremidades Inferiores/genética , Atrofia Muscular Espinal/genética , Adolescente , Sequência de Bases , Criança , Exoma , Feminino , Humanos , Deformidades Congênitas das Extremidades Inferiores/diagnóstico por imagem , Deformidades Congênitas das Extremidades Inferiores/patologia , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Atrofia Muscular Espinal/diagnóstico por imagem , Atrofia Muscular Espinal/patologia , Mutação , Linhagem , Análise de Sequência de DNA , Tomografia Computadorizada por Raios X
9.
Epilepsia ; 53(1): 79-86, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22092154

RESUMO

PURPOSE: The occurrence of acute encephalopathy in children with Dravet syndrome has been reported sporadically. This study clarified the features of acute encephalopathy in children with Dravet syndrome. METHODS: Through the mailing list of the Annual Zao Conference on Pediatric Neurology, we collected 15 patients with clinically diagnosed Dravet syndrome, who had acute encephalopathy, defined as a condition with decreased consciousness with or without other neurologic symptoms, such as seizures, lasting for >24 h in association with infectious symptoms. KEY FINDINGS: There were seven boys and eight girls. A mutation of the SCN1A gene was present in nine (truncation in six and missense in three). The frequency of seizures during the 3 months before the onset of acute encephalopathy was monthly in seven children and none in three. The median age at the onset of acute encephalopathy was 44 months (range 8-184 months). All children had status epilepticus followed by coma as the initial manifestation. Two different distributions of brain lesions were observed on diffusion-weighted images during the acute phase: cerebral cortex-dominant lesions with or without deep gray matter involvement and subcortical-dominant lesions. Four children died; nine survived with severe sequelae, and two had moderate sequelae. SIGNIFICANCE: We must be aware that acute encephalopathy is an important complication in children with Dravet syndrome, and associated with fulminant clinical manifestations and a poor outcome.


Assuntos
Córtex Cerebral/patologia , Deficiência Intelectual/etiologia , Deficiência Intelectual/patologia , Imageamento por Ressonância Magnética , Proteínas do Tecido Nervoso/genética , Convulsões/complicações , Canais de Sódio/genética , Espasmos Infantis/etiologia , Espasmos Infantis/patologia , Doença Aguda , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Deficiência Intelectual/fisiopatologia , Síndrome de Lennox-Gastaut , Masculino , Mutação , Canal de Sódio Disparado por Voltagem NAV1.1 , Convulsões/genética , Convulsões/patologia , Espasmos Infantis/fisiopatologia , Síndrome
11.
Eur J Pediatr ; 170(11): 1481-4, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21932011

RESUMO

Barth syndrome (BTHS) is an X-linked disorder characterized by skeletal myopathy, neutropenia, growth delay, and cardiomyopathy. It is caused by mutations in the tafazzin gene (TAZ). Although early diagnosis is critical to prevent the progression of heart failure, this disease remains unrecognized when heart failure is not clinically significant. Here we report on a 13-year-old boy with no family history of BTHS who was diagnosed with the syndrome in the subclinical stage of heart failure. The clues to the diagnosis of BTHS in this patient were the findings of lipid storage myopathy in the skeletal muscle biopsy, elevated plasma brain natriuretic peptide, and the diagnosis of isolated noncompaction of the ventricular myocardium in echocardiography. Genetic studies of TAZ revealed a disease-causing mutation (p.Gly216Arg) in this patient. Physicians should be aware of the possibility of this disease and carry out genetic studies when it is considered.


Assuntos
Síndrome de Barth/diagnóstico , Insuficiência Cardíaca/prevenção & controle , Adolescente , Diagnóstico Precoce , Ecocardiografia , Humanos , Miocárdio Ventricular não Compactado Isolado/diagnóstico por imagem , Masculino , Músculo Esquelético/patologia , Peptídeo Natriurético Encefálico/sangue
13.
Eur J Pediatr ; 170(11): 1365-7, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21947198

RESUMO

UNLABELLED: Barth syndrome (OMIM #302060) (BTHS) is an X-linked disorder of lipid metabolism characterized by skeletal myopathy, neutropenia, growth delay, and cardiomyopathy. It is caused by mutations in the tafazzin gene (TAZ), which lead to decreased production of an enzyme required to produce cardiolipin, a component of the inner mitochondrial membrane necessary for proper functioning of the electron transport chain. The most common initial presentation of BTHS is significant heart failure due to cardiomyopathy, which is the main cause of death in infancy or childhood. On the other hand, some patients have limited clinical features of BTHS. These patients may be overlooked or misdiagnosed with unclassified congenital myopathy, especially when heart failure is not clinically significant. However, these patients could also develop significant heart failure or life-threatening arrhythmias during or even after childhood. Heart failure in BTHS is often responsive to standard medical therapy, indicating early diagnosis is critical. Diagnostic clues of BTHS in the subclinical stage of heart failure include family histories, findings of lipid storage myopathy in the skeletal muscle biopsy, and elevated plasma brain natriuretic peptide levels. The genetic analysis of TAZ is the only confirmatory method for the diagnosis of BTHS. CONCLUSION: physicians should be aware of the possibility of this disease and carry out genetic studies when it is considered.


Assuntos
Síndrome de Barth , Aciltransferases , Síndrome de Barth/diagnóstico , Síndrome de Barth/genética , Síndrome de Barth/história , Síndrome de Barth/terapia , Criança , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , História do Século XXI , Humanos , Países Baixos , Neurologia/história , Pediatria/história , Prognóstico , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
14.
Am J Med Genet A ; 155A(7): 1511-6, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21671394

RESUMO

Kabuki syndrome is a rare, multiple malformation disorder characterized by a distinctive facial appearance, cardiac anomalies, skeletal abnormalities, and mild to moderate intellectual disability. Simplex cases make up the vast majority of the reported cases with Kabuki syndrome, but parent-to-child transmission in more than a half-dozen instances indicates that it is an autosomal dominant disorder. We recently reported that Kabuki syndrome is caused by mutations in MLL2, a gene that encodes a Trithorax-group histone methyltransferase, a protein important in the epigenetic control of active chromatin states. Here, we report on the screening of 110 families with Kabuki syndrome. MLL2 mutations were found in 81/110 (74%) of families. In simplex cases for which DNA was available from both parents, 25 mutations were confirmed to be de novo, while a transmitted MLL2 mutation was found in two of three familial cases. The majority of variants found to cause Kabuki syndrome were novel nonsense or frameshift mutations that are predicted to result in haploinsufficiency. The clinical characteristics of MLL2 mutation-positive cases did not differ significantly from MLL2 mutation-negative cases with the exception that renal anomalies were more common in MLL2 mutation-positive cases. These results are important for understanding the phenotypic consequences of MLL2 mutations for individuals and their families as well as for providing a basis for the identification of additional genes for Kabuki syndrome.


Assuntos
Anormalidades Múltiplas/genética , Proteínas de Ligação a DNA/genética , Doenças Hematológicas/genética , Mutação/genética , Proteínas de Neoplasias/genética , Doenças Vestibulares/genética , Anormalidades Múltiplas/diagnóstico , Alelos , Face/anormalidades , Ordem dos Genes , Testes Genéticos , Genótipo , Doenças Hematológicas/diagnóstico , Humanos , Fenótipo , Prognóstico , Doenças Vestibulares/diagnóstico
15.
Epilepsia ; 51(12): 2397-405, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20887364

RESUMO

PURPOSE: De novo STXBP1 mutations have been found in individuals with early infantile epileptic encephalopathy with suppression-burst pattern (EIEE). Our aim was to delineate the clinical spectrum of subjects with STXBP1 mutations, and to examine their biologic aspects. METHODS: STXBP1 was analyzed in 29 and 54 cases of cryptogenic EIEE and West syndrome, respectively, as a second cohort. RNA splicing was analyzed in lymphoblastoid cells from a subject harboring a c.663 + 5G>A mutation. Expression of STXBP1 protein with missense mutations was examined in neuroblastoma2A cells. RESULTS: A total of seven novel STXBP1 mutations were found in nine EIEE cases, but not in West syndrome. The mutations include two frameshift mutations, three nonsense mutations, a splicing mutation, and a recurrent missense mutation in three unrelated cases. Including our previous data, 10 of 14 individuals (71%) with STXBP1 aberrations had the onset of spasms after 1 month, suggesting relatively later onset of epileptic spasms. Nonsense-mediated mRNA decay associated with abnormal splicing was demonstrated. Transient expression revealed that STXBP1 proteins with missense mutations resulted in degradation in neuroblastoma2A cells. DISCUSSION: Collectively, STXBP1 aberrations can account for about one-third individuals with EIEE (14 of 43). These genetic and biologic data clearly showed that haploinsufficiency of STXBP1 is the important cause for cryptogenic EIEE.


Assuntos
Eletroencefalografia/estatística & dados numéricos , Epilepsia Generalizada/genética , Haploinsuficiência/genética , Proteínas Munc18/genética , Mutação de Sentido Incorreto/genética , Espasmos Infantis/genética , Encéfalo/fisiopatologia , Epilepsia Generalizada/diagnóstico , Epilepsia Generalizada/fisiopatologia , Feminino , Haploinsuficiência/fisiologia , Humanos , Lactente , Recém-Nascido , Masculino , Mutação de Sentido Incorreto/fisiologia , Espasmos Infantis/diagnóstico , Espasmos Infantis/fisiopatologia
16.
Brain Nerve ; 61(8): 989-93, 2009 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-19697890

RESUMO

Gelastic seizures without hypothalamic hamartoma is a rare forms of epilepsy. Here, we report the case of 4-year-old girl with gelastic seizures. There was no delay in mental or motor development of the patient. The patient exhibited a peculiar seizure pattern that suddenly clung to her mother stiffening her body and an outburst of laughter with no apparent cause. The frequency of the seizures increased over a period of 1 month. Although the brain MRI and interictal EEG showed no abnormality, ictal EEG showed a 14 Hz wave discharge and subsequent slow-wave activity and suppression in bilateral frontal areas. The seizures responded favorably to oral administration of carbamazepine. The induction of the seizures could be related to theophylline administration and emotional excitation.


Assuntos
Emoções/fisiologia , Epilepsias Parciais/etiologia , Epilepsia do Lobo Frontal/etiologia , Anticonvulsivantes/administração & dosagem , Broncodilatadores/efeitos adversos , Carbamazepina/administração & dosagem , Pré-Escolar , Eletroencefalografia , Epilepsias Parciais/diagnóstico , Epilepsias Parciais/tratamento farmacológico , Epilepsia do Lobo Frontal/diagnóstico , Epilepsia do Lobo Frontal/tratamento farmacológico , Feminino , Humanos , Teofilina/efeitos adversos
17.
Clin Pediatr Endocrinol ; 18(2): 65-72, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-24790382

RESUMO

Prolactinomas are rarely diagnosed in children under the age of 10. A 9-yr-old Japanese boy complained of severe headache and progressive visual disturbance. His growth had been retarded for approximately 3 yr, and his serum PRL level was 811.6 ng/ml. Brain magnetic resonance imaging (MRI) revealed an enlarged pituitary (2.8 × 2.6 × 2.1 cm) with heterogeneous enhancement. He was diagnosed as having a macroprolactinoma accompanied by pituitary apoplexy and growth hormone deficiency. A surgical approach was initially undertaken due to the progressive visual deficits, but a residual tumor was observed, and the level of serum PRL was still high after the surgery. Cabergoline was then started, and the dose was gradually increased to 1.5 mg/wk. The serum PRL level decreased from 138.8 ng/ml to 32.5 ng/ml and 17.7 ng/ml after 5 wk and 19 wk, respectively. At 33 wk of cabergoline treatment, brain MRI demonstrated no evidence of the residual tumor. Thereafter, the serum level of PRL decreased to less than 10 ng/ml, and remission was consistently confirmed on repeated MRI. No adverse events have been observed. The present case suggests that cabergoline can be an effective treatment for prolactinomas in prepubertal children as well as in adults.

18.
Neuroimage ; 39(2): 593-9, 2008 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-17962046

RESUMO

A role for gamma-aminobutyric acid (GABA)ergic inhibition in cortical sensory processing is one of the principle concerns of brain research. Angelman syndrome (AS) is thought to be one of the few neurodevelopmental disorders with GABAergic-related genetic involvement. AS results from a functional deficit of the imprinted UBE3A gene, located at 15q11-q13, resulting mainly from a 4-Mb deletion that includes GABA(A) receptor subunit genes. These genes are believed to affect the GABAergic system and modulate the clinical severity of AS. To understand the underlying cortical dysfunction, we have investigated the primary somatosensory-evoked responses in AS patients. Subjects included eleven AS patients with a 15q11-q13 deletion (AS Del), two AS patients without a 15q11-q13 deletion, but with a UBE3A mutation (AS non-Del), six epilepsy patients (non-AS) and eleven normal control subjects. Somatosensory-evoked fields (SEFs) in response to median nerve stimulation were measured by magnetoencephalography. The N1m peak latency in AS Del patients was significantly longer (34.6+/-4.8 ms) than in non-AS patients (19.5+/-1.2 ms, P<0.001) or normal control subjects (18.4+/-1.8 ms, P<0.001). The next component, P1m, was prolonged and ambiguous and was only detected in patients taking clonazepam. In contrast, SEF waveforms of AS non-Del patients were similar to those of control individuals, rather than to AS Del patients. Thus, GABAergic dysfunction in AS Del patients is likely due to hemizygosity of GABA(A) receptor subunit genes, suggesting that GABAergic inhibition plays an important role in synchronous activity of human sensory systems.


Assuntos
Síndrome de Angelman/fisiopatologia , Potenciais Somatossensoriais Evocados/fisiologia , Ácido gama-Aminobutírico/fisiologia , Adolescente , Adulto , Síndrome de Angelman/tratamento farmacológico , Síndrome de Angelman/genética , Anticonvulsivantes/uso terapêutico , Criança , Pré-Escolar , Interpretação Estatística de Dados , Feminino , Deleção de Genes , Humanos , Magnetoencefalografia , Masculino , Nervo Mediano/fisiologia , Córtex Somatossensorial/fisiopatologia , Ubiquitina-Proteína Ligases/genética
19.
Endocr J ; 54(6): 941-4, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18000345

RESUMO

We encountered a Japanese patient of congenital hypothyroidism with severe cerebellum atrophy. The boy was born after 40 weeks of gestation by normal vaginal delivery from nonconsanguineous parents. There were no abnormal physical findings; however neonatal mass screening for congenital hypothyroidism at 5 days of age demonstrated elevated thyrotropin (TSH) level (15.5 microU/ml, normal range 0.54-10.0 microU/ml). He was suspected to have subclinical or mild congenital hypothyroidism (CH). Thus he was treated with L-thyroxine using a regimen that rendered his serum TSH concentration within normal range from 27 days of age. Despite early and adequate treatment, he showed signs of global developmental delay and became gradually hypotonic and exhibited a staggering gait at 3 years of age. Brain magnetic resonance imaging (MRI) demonstrated marked cerebellar atrophy with an intact brainstem. Thyroidal uptake of radioiodide and thyroid gland size were normal, indicating a functional defect only. The relation between congenital hypothyroidism and severe cerebellar atrophy in our patient is not clear. As only a few cases of the combination of CH and cerebellar anomalies have been described previously, cerebellar symptoms in CH should be examined carefully.


Assuntos
Ataxia Cerebelar/patologia , Hipotireoidismo Congênito/patologia , Deficiências do Desenvolvimento/patologia , Tiroxina/uso terapêutico , Ataxia Cerebelar/sangue , Hipotireoidismo Congênito/sangue , Hipotireoidismo Congênito/tratamento farmacológico , Deficiências do Desenvolvimento/sangue , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Tiroxina/sangue , Tri-Iodotironina/sangue
20.
Brain Dev ; 29(8): 529-33, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17383838

RESUMO

Landau-Kleffner syndrome (LKS) is a childhood disorder of unknown etiology characterized by an acquired aphasia and epilepsy. We have performed comprehensive neurofunctional studies on an 8-year-old girl with typical LKS, with the aim of identifying lesions that may be responsible for her condition. 18F-fluoro-D-glucose (FDG) positron emission computed tomography (PET), 11C-Flumazenil (FMZ) PET, 99mTc-hexamethylpropyleneamine oxime single photon emission computed tomography (SPECT) and magnetoencephalography were performed before and after changes to the patient's medication led to a clinical improvement. Interictal SPECT showed hypoperfusion in the left frontal, left temporal, and left occipital lobes. 18F-FDG PET demonstrated a decrease in glucose metabolism medially in both temporal lobes and superiorly in the left temporal lobe. 11C-FMZ PET revealed a deficit in benzodiazepine receptor binding at the tip of the left temporal lobe. Magnetoencephalography demonstrated equivalent current dipoles located superiorly in the left temporal lobe. Our results suggest that the tip of the left temporal lobe plays an important role in the pathogenesis of LKS in our patient.


Assuntos
Síndrome de Landau-Kleffner/metabolismo , Síndrome de Landau-Kleffner/fisiopatologia , Lobo Temporal/metabolismo , Lobo Temporal/fisiopatologia , Anticonvulsivantes/uso terapêutico , Criança , Eletroencefalografia , Feminino , Humanos , Síndrome de Landau-Kleffner/patologia , Imageamento por Ressonância Magnética , Magnetoencefalografia , Tomografia por Emissão de Pósitrons , Convulsões/tratamento farmacológico , Convulsões/etiologia , Tecnécio Tc 99m Exametazima , Lobo Temporal/patologia , Tomografia Computadorizada de Emissão de Fóton Único
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