RESUMO
Presentamos el caso clínico de un niño de 9 años procedente de la región Cusco, con deterioro progresivo del estado neurológico caracterizado por síntomas cerebelosos, asociados a una historia de infecciones respiratorias repetidas y con hallazgos clínicos y de laboratorio que permitieron llegar al diagnóstico de Ataxia-Telangiectasia, enfermedad poco reportada en nuestro país. Se revisa la etiopatogenia, criterios diagnósticos y propuestas terapéuticas disponibles en la actualidad.
We report the case of a 9-year-old from the Cusco region, with progressive deterioration of neurological condition characterized by cerebellar symptoms associated with a history of repeated respiratory infections and clinical and laboratory features that allowed reaching the diagnosis of Ataxia-Telangiectasia, little reported disease in our country. The pathogenesis, diagnostic criteria and therapeutic approaches currently available are reviewed.
Assuntos
Humanos , Masculino , Criança , Ataxia , Ataxia Telangiectasia , Ataxia Telangiectasia/etiologiaRESUMO
Checkpoint response to DNA damage involves the activation of DNA repair and G2 lengthening subpathways. The roles of nibrin (NBS1) and the ATM/ATR kinases in the G2 DNA damage checkpoint, evoked by endogenous and radio-induced DNA damage, were analyzed in control, A-T and NBS lymphoblast cell lines. Short-term responses to G2 treatments were evaluated by recording changes in the yield of chromosomal aberrations in the ensuing mitosis, due to G2 checkpoint adaptation, and also in the duration of G2 itself. The role of ATM/ATR in the G2 checkpoint pathway repairing chromosomal aberrations was unveiled by caffeine inhibition of both kinases in G2. In the control cell lines, nibrin and ATM cooperated to provide optimum G2 repair for endogenous DNA damage. In the A-T cells, ATR kinase substituted successfully for ATM, even though no G2 lengthening occurred. X-ray irradiation (0.4 Gy) in G2 increased chromosomal aberrations and lengthened G2, in both mutant and control cells. However, the repair of radio-induced DNA damage took place only in the controls. It was associated with nibrin-ATM interaction, and ATR did not substitute for ATM. The absence of nibrin prevented the repair of both endogenous and radio-induced DNA damage in the NBS cells and partially affected the induction of G2 lengthening.
Assuntos
/citologia , Dano ao DNA , Dano ao DNA/efeitos da radiação , Proteínas/farmacologia , Proteínas/fisiologia , Proteínas/síntese química , Aberrações Cromossômicas/efeitos da radiação , Ataxia Telangiectasia/etiologia , Ataxia Telangiectasia/genética , Ataxia Telangiectasia/induzido quimicamenteRESUMO
El síndrome de ataxia telangiectasia antes llamado síndrome de Louis-Bar fue descrito en 1941. La enfermedad es autosómica recesiva y se cree que la anormalidad se localiza en la banda 11 del brazo corto de los cromosomas 22-23 (11a 22-23) en donde se sitúa el gen que codifica la proteína esencial en la recombinación utilizada por los genes de la familia de las inmunoglobulinas. El síndrome se caracteriza por ataxia cerebelar progresiva, telangiectasias óculo-cutáneas, enfermedad sinu-bronquial crónica, inmunodeficiencia variable y alta incidencia de tumores como leucemia, adenomas y linfoma no-Hodgkin. A continuación se describe un caso de ataxia-telangiectásica que consultó a nuestra institución.