Videoocular assessment of eye movement activity in an ataxia-telangiectasia: a case study.

PURPOSE: Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by progressive neurological deficits, including prominent oculomotor dysfunction. We report 5 cases of eye movement assessment in children 9-15 years old with A-T. METHODS: Three different oculomotor tasks (gaze holding, visually guided saccades and visual search) were used, and video-oculography was performed. Additionally, the scale for the assessment and rating of ataxia (SARA) score was used to assess severity of the cerebellar ataxia. RESULTS: Unstable gaze holding, nystagmus and saccadic intrusions were found. In addition to psychophysiological assessment results, we provide quantitative analysis of oculomotor activity, revealing a specific abnormal oculomotor pattern, consisting of (i) marked saccade hypermetria, (ii) unstable gaze holding, and (iii) gaze-evoked nystagmus. CONCLUSION: Our study opens the prospect to evaluate efficacy and safety of alternative methods for supporting the patient and improving his/her life quality.

Ataxia-telangiectasia: una revisión desde la etiopatogenia al manejo actual con descripción de casos reportados en Perú / Ataxia telangiectasia: A review from etiopathogenesis to current management with a description of reported cases in Peru

La Ataxia-Telangiectasia (AT) es una rara enfermedad de herencia autosómica recesiva y de afección multisistémica, caracterizada por ataxia progresiva, inmunodeficiencia variable con infecciones recurrentes, riesgo incrementado de neoplasias con o sin telangiectasias óculo-cutáneas. La AT es causada por variantes patogénicas bialélicas en el gen ATM. Su diagnóstico se basa en la sospecha de un cuadro clínico compatible, niveles elevados de alfafetoproteína, atrofia cerebelosa y estudios genéticos. No existe tratamiento curativo de AT y su manejo se basa en medidas de soporte y prevención de complicaciones y asesoramiento genético. En esta revisión, actualizamos la epidemiología, manifestaciones clínicas, diagnóstico y tratamiento de AT incluyendo una búsqueda de casos publicados en el Perú.

Ataxia-Telangiectasia (AT) is a rare autosomal recessive disease with multisystemic involvement, characterized by slowly progressive ataxia, variable immunodeficiency with recurrent infections, increased risk of neoplasms with or without oculocutaneous telangiectasias. AT is caused by biallelic pathogenic variants within the ATM gene. Its diagnosis is based on suspicion of a compatible clinical symptomatology, increased levels of alpha-fetoprotein, cerebellar atrophy, and genetic testing. There is no curative treatment for AT and its management is based on supportive and preventive measures of eventual complications and genetic counseling. This review updates the epidemiology, clinical manifestations, diagnosis, and treatment of AT, including a search for cases published in Peru.

Ataxia-telangiectasia: epidemiology, pathogenesis, clinical phenotype, diagnosis, prognosis and management.

INTRODUCTION: Ataxia-telangiectasia (A-T) is a rare autosomal recessive syndrome characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, variable immunodeficiency, radiosensitivity, and cancer predisposition. Mutations cause A-T in the ataxia telangiectasia mutated (ATM) gene encoding a serine/threonine-protein kinase. AREAS COVERED: The authors reviewed the literature on PubMed, Web of Science, and Scopus databases to collect comprehensive data related to A-T. This review aims to discuss various update aspects of A-T, including epidemiology, pathogenesis, clinical manifestations, diagnosis, prognosis, and management. EXPERT OPINION: A-T as a congenital disorder has phenotypic heterogeneity, and the severity of symptoms in different patients depends on the severity of mutations. This review provides a comprehensive overview of A-T, although some relevant questions about pathogenesis remain unanswered, probably owing to the phenotypic heterogeneity of this monogenic disorder. The presence of various clinical and immunologic manifestations in A-T indicates that the identification of the role of defective ATM in phenotype can be helpful in the better management and treatment of patients in the future.

Assessment of vitamin D status in common variable immunodeficiency or ataxia-telangiectasia patients.

INTRODUCTION AND OBJECTIVES: Vitamin D plays a role in the immune system, however studies regarding this are scarce. This study aimed to evaluate the nutritional status of vitamin D in patients with Common Variable Immunodeficiency (CVID) or Ataxia-Telangiectasia (A-T) and to relate it to body composition, inflammatory and bone metabolism markers. PATIENTS AND METHODS: This is a cross-sectional and controlled study involving 24 patients of both sexes (59.3% male), aged 8-56 years, with CVID (n=15) or A-T (n=9). The following variables were evaluated: body mass index (BMI), 25-hydroxyvitamin D (25 (OH) D), hepatic profile, parathormone, calcium, phosphorus, alkaline phosphatase, interleukin 6 and high-sensitivity C-reactive protein. RESULTS: The median age was 26.0 years. A deficiency of 25 (OH) D was found in four A-T patients (44%) and two CVID patients (13%). Nine patients with CVI (60%) and six with A-T (66.7%) were overweight and underweight, respectively. There was a negative correlation between vitamin D and fat mass in the CVID group, and vitamin D and BMI in the A-T group. Vitamin D was negatively associated with the percentage of total fat among the patients (ß - 0.842, 95% CI: -1.5-0.17, p=0.015), R2=0.21, after adjusting for sex and age. CONCLUSION: Vitamin D deficiency occurred in a quarter of the patients although there was no difference between the patient and the control group; without association with bone and inflammation biomarkers. The percentage of fat and BMI were negatively associated with the concentrations of 25 (OH) D.

Individual Radiosensitivity Assessment of the Families of Ataxia-Telangiectasia Patients by G2-Checkpoint Abrogation.

OBJECTIVES: Ataxia-telangiectasia (A-T) is an autosomal recessive multisystem disorder characterised by cerebellar degeneration, telangiectasia, radiation sensitivity, immunodeficiency, oxidative stress and cancer susceptibility. Epidemiological research has shown that carriers of the heterozygous ataxia-telangiectasia mutated (ATM) gene mutation are radiosensitive to ionising irradiation and have a higher risk of cancers, type 2 diabetes and atherosclerosis. However, there is currently no fast and reliable laboratory-based method to detect heterozygous ATM carriers for family screening and planning purposes. This study therefore aimed to evaluate the ability of a modified G2-assay to identify heterozygous ATM carriers in the families of A-T patients. METHODS: This study took place at the Tehran University of Medical Sciences, Tehran, Iran, between February and December 2017 and included 16 A-T patients, their parents (obligate heterozygotes) and 30 healthy controls. All of the subjects underwent individual radiosensitivity (IRS) assessment using a modified caffeine-treated G2-assay with G2-checkpoint abrogation. RESULTS: The mean IRS of the obligate ATM heterozygotes was significantly higher than the healthy controls (55.13% ± 5.84% versus 39.03% ± 6.95%; P <0.001), but significantly lower than the A-T patients (55.13% ± 5.84% versus 87.39% ± 8.29%; P = 0.001). A receiver operating characteristic (ROC) curve analysis of the G2-assay values indicated high sensitivity and specificity, with an area under the ROC curve of 0.97 (95% confidence interval: 0.95-1.00). CONCLUSION: The modified G2-assay demonstrated adequate precision and relatively high sensitivity and specificity in detecting heterozygous ATM carriers.

The impact of glutamine supplementation on the symptoms of ataxia-telangiectasia: a preclinical assessment.

BACKGROUND: Our previous studies of Alzheimer's disease (AD) suggested that glutamine broadly improves cellular readiness to respond to stress and acts as a neuroprotectant both in vitro and in AD mouse models. We now expand our studies to a second neurodegenerative disease, ataxia-telangiectasia (A-T). Unlike AD, where clinically significant cognitive decline does not typically occur before age 65, A-T symptoms appear in early childhood and are caused exclusively by mutations in the ATM (A-T mutated) gene. RESULTS: Genetically ATM-deficient mice and wild type littermates were maintained with or without 4 % glutamine in their drinking water for several weeks. In ATM mutants, glutamine supplementation restored serum glutamine and glucose levels and reduced body weight loss. Lost neurophysiological function assessed through the magnitude of hippocampal long term potentiation was significantly restored. Glutamine supplemented mice also showed reduced thymus pathology and, remarkably, a full one-third extension of lifespan. In vitro assays revealed that ATM-deficient cells are more sensitive to glutamine deprivation, while supra-molar glutamine (8 mM) partially rescued the reduction of BDNF expression and HDAC4 nuclear translocation of genetically mutant Atm(-/-) neurons. Analysis of microarray data suggested that glutamine metabolism is significantly altered in human A-T brains as well. CONCLUSION: Glutamine is a powerful part of an organism's internal environment. Changes in its concentrations can have a huge impact on the function of all organ systems, especially the brain. Glutamine supplementation thus bears consideration as a therapeutic strategy for the treatment of human A-T and perhaps other neurodegenerative diseases.