462Ataxia-telangiectasia (A-T) is an autosomal recessive genomic instability syndrome characterized by progressive cerebellar ataxia, oculocutaneous telangiectasias, immunodeficiency, hypersensitivity to ionizing radiation, and cancer predisposition, with lymphoid malignancies predominating in the first two decades of life [1][2][3][4][5][6][7][8][9][10] . Mutations in the Ataxiatelangiectasia mutated (ATM) gene result in markedly decreased or absent levels of ATM kinase, a protein that phosphorylates many downstream targets. A deficiency of ATM kinase leads to cell cycle defects, faulty repair of DNA damage, defective apoptosis, and poor responses to oxidative stress 1,3,11 .ABSTRACT: Background: The onset of progressive cerebellar ataxia in early childhood is considered a key feature of ataxiatelangiectasia (A-T), accompanied by ocular apraxia, telangiectasias, immunodeficiency, cancer susceptibility and hypersensitivity to ionizing radiation. Methods: We describe the clinical features and course of three Mennonite children who were diagnosed with A-T following the completion of therapy for lymphoid malignancies. Results: Prior to cancer therapy, all had non-progressive atypical neurological abnormalities, with onset by age 30 months, including dysarthria, dyskinesia, hypotonia and/or dystonia, without telangiectasias. Cerebellar ataxia was noted in only one of the children and was mild until his death at age eight years. None had severe infections. All three children were "cured" of their lymphoid malignancies, but experienced severe adverse effects from the treatments administered. The two children who received cranial irradiation developed supratentorial primitive neuroectodermal tumors of the brain, an association not previously described, with fatal outcomes. Conclusions: The range of neurological presentations of A-T is broad. Ataxia and telangiectasias may be minimal or absent and the course seemingly non-progressive. The diagnosis of A-T should be considered in all children with neuromotor dysfunction or peripheral neuropathy, particularly those who develop lymphoid malignancies. The consequences of missing the diagnosis may be dire. Radiation therapy and radiomimetic drugs should be avoided in individuals with A-T. RÉSUMÉ: Mode de présentation atypique et toxicité du traitement anticancéreux chez les patients atteints d'ataxie-télangiectasie. Contexte :L'apparition d'une ataxie cérébelleuse progressive dans la petite enfance est considérée comme une manifestation clé de l'ataxie-télangiectasie (A-T), accompagnée d'apraxie oculaire, de télangiectasies, d'un déficit immunitaire, de susceptibilité au cancer et d'hypersensibilité aux radiations ionisantes. Méthodes : Nous décrivons les manifestations cliniques et l'évolution chez trois enfants mennonites chez qui un diagnostic d'A-T a été posé après un traitement pour cancer lymphoïde. Résultats : Avant le traitement anticancéreux, tous présentaient des anomalies neurologiques atypiques non évolutives, dont l'âge de début se situait vers 30 mois, soit de ...

No abstract

Acute necrotizing encephalopathy (ANE) in childhood was originally described in the Far East. 1,2 Disease onset is commonly preceded by a viral illness. 1,3 Neurological deterioration occurs abruptly and rapidly. Neuroimaging is characteristic. 4 Steroids and less commonly intravenous immunoglobulins have been used with variable outcomes. 5 More recently, cases have been reported from Europe and North America. 3,6,7 Here we present the first report of recurrent ANE in a Canadian Aboriginal child. CASE REPORT A previously healthy 34-month-old aboriginal Canadian boy from northern Manitoba presented with a four day history of cough and fever, and two day history of headache and irritability. He was sleepy the day prior to his presentation. There was no history of trauma, travel, rash or toxic ingestion. He did not have seizures. He was initially seen at the local hospital. His Glasgow Coma Scale was six. He was intubated, ventilated, and transferred to the Pediatric Intensive Care Unit at our hospital where he was started empirically on intravenous Cefotaxime, Vancomycin and Acyclovir. His past medical history is unremarkable. The mother was well during pregnancy. He was born at thirty six weeks gestation following an uneventful pregnancy and spontaneous vaginal delivery. His birth weight was 2.7 kg. His development was normal prior to his presentation. The parents are of Canadian Aboriginal Cree descent and are nonconsanguineous. Serial investigations were done including, full blood count (CBC), electrolytes, ammonia, glucose, liver function tests, cortisol, ACTH, TSH, T3, T4, vitamin B 12 , lead, antithyroid antibodies, ANCA, ANA, toxicology screen, capillary lactic acid, plasma amino acids, plasma very long chain fatty acids, whole blood palmitate oxidation assay (a rapid screening test for fatty acids oxidation defects), free and total serum carnitine levels, acylcarnitine profile, lysosomal enzymes assay panel, blood cultures; urine amino and organic acids; cerebrospinal fluid (CSF) glucose, protein, cell count, lactic acid, amino acids, oligoclonal bands, bacterial, fungal, and viral cultures including human herpes viruses (lumbar puncture was done twice, four days apart); and stool for Enteroviruses. The results were all normal except for mild elevation of CSF protein on the first lumbar puncture at 0.52g/L (normal range: 0.15-0.4). The results of the oligoclonal bands were negative; however, there was a systemic immune reaction associated with CSF abnormality. The electroencephalogram (EEG) showed slowing in background activity consistent with an encephalopathic process.