RESUMO
Early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH) is a neurodegenerative disorder caused by mutation in the aprataxin (APTX)-coding gene APTX, which is involved in DNA single-strand break repair (SSBR). The neurological abnormalities associated with EAOH are similar to those observed in patients with ataxia-telangiectasia. However, the immunological abnormalities in patients with EAOH have not been described. In this study, we report that EAOH patients have immunological abnormalities, including lymphopenia; decreased levels of CD4+ T-cells, CD8+ T-cells, and B-cells; hypogammaglobulinemia; low T-cell recombination excision circles and kappa-deleting element recombination circles; and oligoclonality of T-cell receptor ß-chain variable repertoire. These immunological abnormalities vary among the EAOH patients. Additionally, mild radiosensitivity in the lymphocytes obtained from the patients with EAOH was demonstrated. These findings suggested that the immunological abnormalities and mild radiosensitivity evident in patients with EAOH could be probably caused by the DNA repair defects.
Assuntos
Apraxias/imunologia , Ataxia Cerebelar/congênito , Hipoalbuminemia/imunologia , Adolescente , Adulto , Apraxias/genética , Apraxias/metabolismo , Estudos de Casos e Controles , Ataxia Cerebelar/genética , Ataxia Cerebelar/imunologia , Ataxia Cerebelar/metabolismo , Criança , Quebras de DNA de Cadeia Simples , Reparo do DNA/genética , Reparo do DNA/efeitos da radiação , Proteínas de Ligação a DNA/genética , Feminino , Genes Codificadores dos Receptores de Linfócitos T , Variação Genética , Humanos , Hipoalbuminemia/genética , Hipoalbuminemia/metabolismo , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Nucleares/genética , Tolerância a Radiação/genética , Tolerância a Radiação/imunologia , Linfócitos T/imunologia , Adulto JovemRESUMO
A woman with Sjögren syndrome manifesting as aphasia with a left deep cerebral white matter lesion tested positive for anti-aquaporin 4 (AQP4) antibody. Open biopsy of the lesion revealed active demyelination with edematous changes and the preservation of most axons, indicating a non-necrotic demyelinating lesion. Immunostaining for AQP4 was diffusely lost, whereas the loss of glial fibrillary acidic protein immunostaining was limited but with highly degenerated astrocytic foot processes in perivascular areas. These results suggested neuromyelitis optica spectrum disorder (NMOSD) pathology rather than Sjögren-related vasculitis. Only cerebral cortical symptoms with a cerebral white matter lesion could be observed in NMOSDs.
Assuntos
Afasia/etiologia , Apraxias/etiologia , Córtex Cerebral/patologia , Leucoencefalopatias/patologia , Neuromielite Óptica/patologia , Síndrome de Sjogren/complicações , Substância Branca/patologia , Afasia/diagnóstico , Afasia/imunologia , Apraxias/diagnóstico , Apraxias/imunologia , Aquaporina 4/imunologia , Autoanticorpos/análise , Biópsia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/imunologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imuno-Histoquímica , Leucoencefalopatias/complicações , Leucoencefalopatias/tratamento farmacológico , Leucoencefalopatias/imunologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Neuromielite Óptica/complicações , Neuromielite Óptica/tratamento farmacológico , Neuromielite Óptica/imunologia , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/imunologia , Resultado do Tratamento , Substância Branca/efeitos dos fármacos , Substância Branca/imunologiaRESUMO
Mutations in senataxin have been described recently in 24 cases of French-Canadian descent with ataxia-oculomotor apraxia 2. This recessive ataxia is associated with an elevation in alpha-fetoprotein as in ataxia-telangiectasia. Because ataxia-telangiectasia cells are highly radiosensitive, we used a colony survival assay to measure the radiosensitivity of lymphoblastoid cell lines derived from five French-Canadian patients with ataxia-oculomotor apraxia 2. Two were homozygous for the common French-Canadian L1976R SETX missense mutation; the three others were compound heterozygotes for the common mutation and three different missense mutations. Overall, lymphoblastoid cell lines derived from these cases did not show significant variation from a normal response to 1 Gray of ionizing radiation but the two patients who were homozygous for the common L1976R mutation fell in the intermediate or non-diagnostic range.
Assuntos
Apraxias/diagnóstico , Ataxia/diagnóstico , Transtornos da Motilidade Ocular/diagnóstico , Adolescente , Apraxias/genética , Apraxias/imunologia , Ataxia/genética , Ataxia/imunologia , Linhagem Celular , Criança , Ensaio de Unidades Formadoras de Colônias/métodos , DNA Helicases , Análise Mutacional de DNA , Predisposição Genética para Doença/genética , Humanos , Linfócitos/fisiologia , Linfócitos/efeitos da radiação , Enzimas Multifuncionais , Mutação/genética , Neoplasias/diagnóstico , Neoplasias/genética , Transtornos da Motilidade Ocular/genética , Transtornos da Motilidade Ocular/imunologia , Prognóstico , Quebeque/etnologia , RNA Helicases/genética , Radiação Ionizante , alfa-Fetoproteínas/genéticaRESUMO
Rett syndrome (RTT) is neurodevelopmental disorder with the onset at critical period of postnatal ontogenesis and age dependent occurrence of clinical manifestations. The aim of the present study was to investigate possible correlations of the age of disease onset with clinical manifestations at the stage 3 of illness and neurobiological parameters. The study was carried out in 38 girls with classical RTT, aged from 3 to 7 years, and twenty and eighteen patients with the disease onset before and after the age of one year were divided into the groups 1 and 2 (Gr1 and Gr2), respectively. Quantitative EEG (QEEG) and measurement of the serum levels of autoantibodies (AAB) to nerve growth factor (NGF) were performed. Clinically, speech and motor functions were significantly more severely affected in the Gr1 than in the Gr2. In QEEG, spectral density of theta activity was significantly higher in Gr1 than in the Gr2. The titer of AAB to NGF was significantly increased in comparison with healthy controls, and the titer in Gr2 was higher than in Gr1. The data obtained suggests that patients with the classical RTT can be divided into subgroups according to the age of disease onset and genetic factors such as mosaicism of MeCP2 mutation may be associated with the heterogeneity of phenotype in RTT patients.
