RESUMO
BACKGROUND: Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder associated with spinal motor neuron loss and characterized by generalized muscle weakness. Only a few reports exist on SMA epidemiology in Japan. Additionally, nusinersen recently became available as a treatment for this condition. We estimated the prevalence of each type of SMA on Shikoku, Japan's fourth-largest major island. METHODS: We sent a questionnaire to all 131 hospitals in Shikoku that have pediatrics or neurology departments from March to September 2019, asking whether each hospital had SMA patients at that time. If so, we sent a second questionnaire to obtain more detailed information on the clinical data and treatment of each patient. RESULTS: A total of 117 hospitals (89.3%) responded to our first questionnaire, and 21 SMA patients were reported, 16 of whom had homozygous deletion of SMN1. Of the 21, nine had SMA type 1, five were type 2, five were type 3, one was type 4, and one was unidentified. The estimated prevalence for all instances of SMA and 5q-SMA was 0.56 and 0.43 per 100,000 people, respectively. Thirteen patients had received nusinersen therapy. Its outcomes varied from no obvious effects and being unable to sit to being able to sit independently. CONCLUSION: Our data showed the prevalence of SMA types 2 and 3 was relatively low on Shikoku compared with previous reports from other countries, suggesting delayed diagnosis may affect the results. Remaining motor function may be one predicting factor. Greater awareness of SMA among clinicians and patients seems necessary for more accurate epidemiological studies.
Assuntos
Atrofia Muscular Espinal/epidemiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Homozigoto , Humanos , Lactente , Recém-Nascido , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Atrofia Muscular Espinal/genética , Mutação/genética , Oligonucleotídeos/uso terapêutico , Prevalência , Deleção de Sequência/genética , Inquéritos e Questionários , Proteína 1 de Sobrevivência do Neurônio Motor/genética , Proteína 2 de Sobrevivência do Neurônio Motor/genética , Adulto JovemRESUMO
BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by homozygous mutations in the SMN1 gene. SMA has long been known to be the most common genetic cause of infant mortality. However, there have been no reports on the epidemiology of infantile SMA (types 1 and 2) based on genetic testing in Japan. In this study, we estimated the incidence of infantile SMA on Shikoku Island, which is a main island of Japan and consists of four prefectures: Ehime, Kagawa, Tokushima and Kochi. METHODS: A questionnaire was sent to 91 hospitals on Shikoku Island to investigate the number of SMA infants born from 2011 to 2015. A second questionnaire was then sent to confirm the diagnoses of SMA based on clinical and genetic features. RESULTS: Responses were received from all of the hospitals, and four patients were diagnosed with infantile SMA among 147,950 live births. We estimated the incidence of infantile SMA patients as 2.7 per 100,000 live births (95% confidence interval, 0.1-5.4). A comparison of the four prefectures indicated that the incidence of infantile SMA was significantly higher in Ehime Prefecture than in the other three prefectures; 5.6 per 100,000 live births (95% confidence interval, -0.7 to 11.9) in Ehime Prefecture and 1.1 per 100,000 live births (95% confidence interval, -1.0 to 3.1) in the other prefectures. CONCLUSION: We estimated the incidence of infantile SMA in an isolated area of Japan. For more precise determination of the incidence of infantile SMA, further studies that include neonatal screening will be needed.
Assuntos
Atrofias Musculares Espinais da Infância/epidemiologia , Feminino , Humanos , Incidência , Lactente , Japão/epidemiologia , Masculino , Atrofias Musculares Espinais da Infância/genética , Proteína 1 de Sobrevivência do Neurônio Motor/genética , Proteína 2 de Sobrevivência do Neurônio Motor/genéticaRESUMO
Artificial respiration by tracheostomy is necessary for long-term survival in spinal muscular atrophy (SMA) Type I patients. There are two types of tracheostomy: i )simple tracheostomy and ii) tracheostomy plus aspiration prevention surgery, including laryngotracheal separation. We experienced three cases of SMA type I patients that had good outcomes after undergoing laryngotracheal separation. The patients' ages at onset were 14 days, two months and one and a half months. Laryngotracheal separation was performed at five months, seven months, and 15 years and five months respectively, and the times from diagnosis to surgery were a month, three months and 15 years. The aspiration pneumonia disappeared in all three cases. This study suggests that laryngotracheal separation is an effective surgery to prevent aspiration in SMA type I cases, and also contributes to the improved quality of life of patients and their families.
Assuntos
Laringe/cirurgia , Atrofias Musculares Espinais da Infância/cirurgia , Traqueostomia , Traqueotomia , Adolescente , Humanos , Lactente , Masculino , Qualidade de VidaRESUMO
We report two female infants with early myoclonic encephalopathy (EME) whose intractable focal seizures were suppressed with lidocaine and carbamazepine (CBZ). Although EME is a form of early-onset epileptic encephalopathy characterised by myoclonus and focal seizures that are highly resistant to treatment, lidocaine and CBZ may prove effective in treating this disorder. Future studies should be performed in order to determine whether there are common specific mechanisms of seizure generation related to the sodium channel in these patients.
Assuntos
Anestésicos Locais/uso terapêutico , Anticonvulsivantes/uso terapêutico , Carbamazepina/uso terapêutico , Lidocaína/uso terapêutico , Espasmos Infantis/tratamento farmacológico , Encéfalo/patologia , Eletroencefalografia , Epilepsia Tônico-Clônica/tratamento farmacológico , Epilepsia Tônico-Clônica/etiologia , Feminino , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Convulsões/tratamento farmacológico , Convulsões/etiologia , Espasmo/etiologia , Resultado do TratamentoRESUMO
PURPOSE: Our aim was to develop a screening test to predict Dravet syndrome before the first birthday based on the clinical characteristics of infants and the SCN1A mutation analysis. METHODS: Ninety-six patients who experienced febrile seizures before the age of one were enrolled. The patients were divided into two groups-the Dravet syndrome group (n = 46) and the non-Dravet syndrome group (n = 50). We compared the clinical characteristics before one year of age of the two groups. We analyzed all coding exons of the SCN1A gene by the direct sequencing method. Scores from 0 to 3 were assigned to each risk factor based on the odds ratio and p-value. RESULTS: An age of onset of febrile seizure
Assuntos
Análise Mutacional de DNA/métodos , Testes Genéticos/métodos , Mutação de Sentido Incorreto/genética , Proteínas do Tecido Nervoso/genética , Convulsões Febris/diagnóstico , Canais de Sódio/genética , Adolescente , Fatores Etários , Idade de Início , Assistência Ambulatorial , Criança , Eletroencefalografia/estatística & dados numéricos , Feminino , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Humanos , Incidência , Japão/epidemiologia , Masculino , Canal de Sódio Disparado por Voltagem NAV1.1 , Pediatria/métodos , Valor Preditivo dos Testes , Probabilidade , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Convulsões Febris/epidemiologia , Convulsões Febris/genética , Síndrome , Escalas de WechslerRESUMO
Eight mutations of the alpha subunit of beta-hexosaminidase A gene ( HEXA) were identified in eight patients with GM2 gangliosidosis variant B. They were five missense mutations, two splice-site mutations, and one two-base deletion. Five of them, R252L (CGT-->CTT), N295S (AAT-->AAC), W420C (TGG-->TGT), IVS 13, +2A-->C, and del 265-266AC (exon 2), were novel mutations responsible for infantile acute form of GM2 gangliosidosis. Two missense mutations, R499H and R499C, were found in one allele of two patients with attenuated phenotypes. The patient with R499C showed a late infantile form, and the other patient with R499H showed a juvenile form. These two mutations have been reported previously in the patients of other ethnic groups, and they have been known to cause attenuated phenotypes. The milder phenotypes of GM2 gangliosidosis variant B, different from the infantile acute form, have not been reported so far in Japan, and this is the first report of Japanese patients with attenuated phenotypes and their molecular analysis.
Assuntos
Mutação de Sentido Incorreto , Doença de Tay-Sachs/genética , beta-N-Acetil-Hexosaminidases/genética , Doença Aguda , Povo Asiático/genética , Criança , Códon , Feminino , Hexosaminidase A , Humanos , Lactente , Masculino , Fenótipo , Doença de Tay-Sachs/enzimologia , Doença de Tay-Sachs/patologiaRESUMO
We classified 28 patients with severe myoclonic epilepsy in infancy (SME) according to the presence or absence of myoclonic seizures and/or atypical absences. Eleven of the patients had myoclonic seizures and/or atypical absences, and we refer to this condition as 'typical SME (TSME)'. Seventeen of the patients had only segmental myoclonias, and we refer to this condition as 'borderline SME (BSME)'. We then analyzed the electroclinical and genetic characteristics of these two groups. Ten of the 11 TSME patients had a photoparoxysmal response at some time during their clinical course, while none of the BSME patients showed this response. TSME and BSME showed a significant difference in regard to gender ratio: female dominance in TSME and male dominance in BSME (P=0.008). The detection rate of the voltage-gated sodium channel alpha1-subunit (SCN1A) gene mutations was 72.7 and 88.2% in TSME and BSME, respectively. There was no difference in the type or rate of mutation between TSME and BSME. We conclude that TSME and BSME show distinct differences in photoparoxysmal response and gender, which might be caused by some genetic mechanism(s) other than the SCN1A gene mutation.