RESUMO
BACKGROUND: Recently we showed that antibodies to myelin oligodendrocyte glycoprotein (MOG) can be found in aquaporin-4 (AQP4)-immunoglobulin (IgG) seronegative pediatric and adult patients with definite and high-risk neuromyelitis optica (NMO). OBJECTIVE: The purpose of this study was to describe the clinical characteristics and temporal dynamics of MOG-IgG in AQP4-IgG seronegative pediatric patients presenting with definite NMO. METHODS: Children with definite NMO who were referred for further testing of serum antibodies for AQP4 and MOG with a cell-based assay were included in this study. Clinical disease course, cerebrospinal fluid and magnetic resonance imaging (MRI) studies of these patients were reviewed. RESULTS: Between 2008 and 2012 eight children who fulfilled the diagnostic criteria of definite NMO were recruited. Two children with definite NMO tested positive for AQP4-IgG but were negative for MOG-IgG antibodies. Three children had an absence of AQP4-IgG and MOG-IgG antibodies. Three children with definite NMO had high titers of serum MOG-IgG antibodies (≥1: 160), but no AQP4-directed humoral immune response. Longitudinal analysis of serum samples of the latter three children showed persisting high MOG-IgG titers over time. CONCLUSION: Pediatric patients presenting with clinical symptoms and MRI findings highly suggestive of NMO but with high and persisting MOG-IgG antibody titers are most likely to represent a distinct subgroup of acute demyelinating diseases with important clinical and therapeutic implications.
Assuntos
Autoanticorpos/sangue , Glicoproteína Mielina-Oligodendrócito/imunologia , Neuromielite Óptica/sangue , Neuromielite Óptica/imunologia , Adolescente , Adulto , Aquaporina 4/imunologia , Autoanticorpos/imunologia , Autoantígenos/imunologia , Criança , Feminino , Humanos , Imunoglobulina G/imunologia , Imageamento por Ressonância Magnética , MasculinoRESUMO
PURPOSE: Mutations in the PRRT2 gene have been recently described as a cause of paroxysmal kinesigenic dyskinesia, infantile convulsions with choreoathetosis syndrome and, less often, infantile convulsions. We have analysed the frequency of PRRT2 mutations in families with benign familial infantile convulsions without paroxysmal kinesigenic dyskinesia. METHODS AND RESULTS: Direct sequencing of the coding region identified the PRRT2 mutation c.649dupC in 5/5 families with infantile convulsions. The mutation was present in 23 family members, of which 18 were clinically affected and 2 were obligate carriers. The affected carriers of this mutation presented with different types of epileptic seizures during early childhood but did not develop additional neurological symptoms later in life. CONCLUSION: Our data demonstrate that the PRRT2 mutation c.649dupC is a frequent cause of benign familial infantile convulsions.
Assuntos
Epilepsia Neonatal Benigna/diagnóstico , Epilepsia Neonatal Benigna/genética , Proteínas de Membrana/genética , Mutação/genética , Proteínas do Tecido Nervoso/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Discinesias/diagnóstico , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Linhagem , Adulto JovemAssuntos
Cromossomos Humanos X , Glicerol Quinase/deficiência , Glicerol/urina , Doenças do Sistema Nervoso/genética , Aberrações dos Cromossomos Sexuais , Pré-Escolar , Dieta com Restrição de Gorduras , Humanos , Hiperlipoproteinemia Tipo IV/dietoterapia , Hiperlipoproteinemia Tipo IV/genética , Lactente , Recém-Nascido , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/dietoterapia , Fenótipo , Fatores de Risco , Morte Súbita do Lactente/genéticaAssuntos
Encéfalo/anormalidades , Anormalidades do Olho/genética , Distrofias Musculares/genética , Mutação de Sentido Incorreto , Proteínas/genética , Encéfalo/patologia , Criança , Feminino , Predisposição Genética para Doença , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Músculo Esquelético , Distrofias Musculares/diagnóstico , Pentosiltransferases , SíndromeRESUMO
Glut-1 deficiency syndrome was first described in 1991 as a sporadic clinical condition, later shown to be the result of haploinsufficiency. We now report a family with Glut-1 deficiency syndrome affecting 5 members over 3 generations. The syndrome behaves as an autosomal dominant condition. Affected family members manifested mild to severe seizures, developmental delay, ataxia, hypoglycorrhachia, and decreased erythrocyte 3-O-methyl-D-glucose uptake. Seizure frequency and severity were aggravated by fasting, and responded to a carbohydrate load. Glut-1 immunoreactivity in erythrocyte membranes was normal. A heterozygous R126H missense mutation was identified in the 3 patients available for testing, 2 brothers (Generation 3) and their mother (Generation 2). The sister and her father were clinically and genotypically normal. In vitro mutagenesis studies in Xenopus laevis oocytes demonstrated significant decreases in the transport of 3-O-methyl-D-glucose and dehydroascorbic acid. Xenopus oocyte membranes expressed high amounts of the R126H mutant Glut-1. Kinetic analysis indicated that replacement of arginine-126 by histidine in the mutant Glut-1 resulted in a lower Vmax. These studies demonstrate the pathogenicity of the R126H missense mutation and transmission of Glut-1 deficiency syndrome as an autosomal dominant trait.
Assuntos
Epilepsia/genética , Proteínas de Transporte de Monossacarídeos/genética , Mutação de Sentido Incorreto , 3-O-Metilglucose/farmacocinética , Sequência de Aminoácidos , Animais , Criança , Deficiências do Desenvolvimento/genética , Eritrócitos/metabolismo , Saúde da Família , Feminino , Genes Dominantes , Transportador de Glucose Tipo 1 , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Proteínas de Transporte de Monossacarídeos/deficiência , Proteínas de Transporte de Monossacarídeos/metabolismo , Oócitos , Linhagem , Xenopus laevisRESUMO
OBJECTIVE: We tested the hypothesis that healthy preterm infants have attenuated ventilatory responses to hypercapnia, associated with a decreased rib cage contribution to ventilation, in the supine versus prone position. STUDY DESIGN: We elicited hypercapnic ventilatory responses from 19 healthy preterm infants (postconceptional age 35 +/- 1 weeks) who were being prepared for hospital discharge. The O2 saturation was continuously monitored. Before and during CO2 rebreathing, ventilation was measured with a nasal mask pneumotachygraph and was derived from chest wall motion as determined by respiratory inductance plethysmograph. This measuring method allowed us to compare both ventilation and the percentage rib cage contribution to ventilation between supine and prone positions. Statistical analysis employed analysis of variance with repeated measures. RESULTS: The supine position was associated with a higher respiratory rate (p < 0.02) and lower O2 saturation (p < 0.007) than the prone position. The increase in ventilation in response to hypercapnia was lower in the supine than in the prone position. This was statistically significant for the respiratory inductance plethysmograph (p < 0.008) but not the pneumotachygraph (p = 0.077), and was associated with a smaller rib cage contribution to ventilation in the supine than in the prone position (p < 0.0001). CONCLUSION: Respiratory control may be vulnerable when healthy preterm infants are placed supine. Widespread avoidance of the prone position may not be appropriate for such patients.
Assuntos
Hipercapnia/prevenção & controle , Recém-Nascido Prematuro , Respiração , Decúbito Dorsal , Dióxido de Carbono/análise , Feminino , Humanos , Recém-Nascido , Masculino , Decúbito Ventral , Ventilação Pulmonar , Testes de Função Respiratória , Sono , Morte Súbita do Lactente/prevenção & controleRESUMO
Defects in the mitochondrial energy generating system in patients with a mitochondrial myopathy are known to be localized in various enzyme complexes involved in energy production. Such a defect may exist at the level of mitochondrial creatine kinase (Mi-CK). On that account we have developed a method for measurement of the enzyme activity in human skeletal muscle biopsy material (greater than 10 mg). Interfering creatine kinase isoenzymes are removed by anion exchange and affinity chromatography. The activity of Mi-CK in reference skeletal muscle homogenates amounts to 240 +/- 88 mU/mg protein (30 +/- 8.0 mU/mg wet weight).