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Objective: Ataxia telangiectasia (AT) is a rare genetic, multi-system disorder characterized by neurodegeneration, chromosome instability, B and T cell immunodeficiency and a predisposition to cancer. We examined immunologic parameters reflecting cell development and proliferation and their relevancy to the clinical phenotype in affected individuals., Patients and Methods: AT patients from the AT National Clinic in Israel underwent immunological investigation. Their T and B cell workup included lymphocyte subset counts, immunoglobulin levels, responses to mitogenic stimulations, TCR-Vβ families and BCR immunoglobulin heavy chain spectratyping, TCR rearrangement excision circles (TRECs) and Kappa-deleting recombination excision circles (KRECs)., Results: Thirty-seven AT patients (median age 12.7 years, range 4.2-25.1) were evaluated. CD20 B and CD3 T lymphocytes were decreased in 67 % and 64 % of the patients, respectively, while only 33 % of the patients had reduced lymphoproliferative responses. Almost all AT patients displayed extremely low TRECs and KRECs levels, irrespective of their age. Those levels were correlated to one another and to the amounts of CD3+ and CD20+ cells, respectively. Abnormal TCR-Vβ repertoires were found with different degrees of clonality or reduced expression in these AT patients. There was no clear clustering of expansions to specific TCR-Vβ genes. PCR spectratyping analysis of the FR2 IgH BCR gene rearrangements in peripheral blood was abnormal in 50 % of the patients., Conclusion: The immunodeficiency associated with AT is combined, remains low over time and not progressive. It is characterized by low TREC and KREC copies suggestive of abnormal T and B cell neogenesis.

Background: Previous reports on the cutaneous manifestations of ataxia-telangiectasia (A-T) have relied on data from small series, in patients not genetically tested for A-T., Objective: The aim of our study was to characterize the dermatologic manifestations in patients with A-T followed up at the national A-T clinic in Israel., Methods: This retrospective cross-sectional study included 32 patients followed up at a multidisciplinary A-T clinic from 2010 to 2012. Complete skin examination was done by a single dermatologist. Information about mutations and neurologic status was extracted from the patients' charts. Relevant demographic, clinical, and laboratory characteristics of all patients were collected and summarized., Results: Of the 32 patients, 97% had ocular telangiectasia, the hallmark of the disease. Telangiectasia on other body parts was less frequent. Pigmentary anomalies included café-au-lait macules (84%), hypopigmented macules (44%), and melanocytic nevi (37%). A facial papulosquamous rash was found in 41% of cases. Other manifestations included hypertrichosis and birdlike facies. We did not observe premature hair graying or poliosis. No genotype-phenotype correlation was found in terms of skin manifestations., Limitations: There was a modest sample size, because of the rarity of the disease., Conclusion: Recognition of the ocular and dermatologic manifestations of A-T can facilitate early diagnosis in a child with neurologic deterioration., (Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Objective: To define the neurologic characteristics and course of ataxia-telangiectasia (A-T)., Study Design: Retrospective cross-sectional chart study of 57 children (ages 2 to 19 years) followed at an A-T clinic. Cerebellar and extracerebellar symptoms were graded according to degree of functional impairment. Head circumferences were plotted from the charts and z-scores were calculated and compared with that of family members., Results: Ataxia was present in 87.7%, followed by dysarthria (82.1%), dysmetria (75.4%), bradykinesia (69.2%), hyperkinetic movements (58.9%), and dystonia (15.8%). All features aggravated with age. The most striking clinical observation in our patients was low head circumference (z-score below 1), which was present in 60.9%; 17% had true microcephaly (z-score below 2). Microcephaly appeared postnatally, was proportionate to height and weight, and did not correlate with severity of ataxia or genotype., Conclusions: In addition to cerebellar ataxia, extrapyramidal symptoms, especially bradykinesia, were frequent and disabling. Microcephaly is an integral part of A-T; understanding its pathogenesis may shed light on the mechanism by which ATM mutation causes dysfunction in the nervous system., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Objectives: To explore the feasibility and validity of forced spirometry in patients with ataxia telangiectasia (A-T)., Study Design: Twenty-eight patients (aged 3.7-19.3 years) performed spirometry on 47 occasions. Parameters studied were technical quality and relation to: predicted values, pulmonary illness., Results: Start of test criteria for correct expiratory effort was significantly prolonged (183 ± 115 ms; P < 0.001). The rise-time to peak flow in children free of respiratory symptoms (Group-FRS; n = 8) increased by 16.2 ± 12.5 ms/year above recommended and in children having recurrent infections (n = 8) 30.4 ± 16.1 ms/year, P < 0.01. Expiration-time was significantly shorter than requested (1.21 ± 0.47 sec) and was ended abruptly in 57% of the patients. FEV(1) could not be established by 8/20 patients. The intra-subject reproducibility met criteria (4.4 ± 2.7%, 5.2 ± 2.8%, 2.9 ± 3.2%, 6.3 ± 5.3%, for FVC, FEV(0.5), PEF, FEF(25-75), respectively). Group-FRS showed yearly deterioration in FVC of 2.2%, while patients with hyper-reactive airways (Group-HRA; n =12) had a deterioration rate of 3.6%/year. FEV(0.5) deterioration rate was similar in both groups (2.2 and 2.0, respectively), but baseline values in Group-HRA were significantly lower than those of Group-FRS (P = 0.029) in similar young ages, indicating airway obstruction at early ages in Group-HRA. FEV(0.5) values deterioration also correlated with body mass index (P < 0.017)., Conclusion: Forced spirometry in A-T patients is reproducible and has a distinct pattern, although curves do not meet other recommendations for acceptable criteria. The study insinuates that a rapid deterioration in lung function occurs in A-T patients with recurrent respiratory infection, suggesting that early intervention may prevent further deterioration or improve their lung function. Further studies are needed to confirm our results., (© 2010 Wiley-Liss, Inc.)

Introduction: Lung disease is a significant cause of the short life span of ataxia telangiectasia (A-T) patients. Objective lung function measurements are difficult to achieve in A-T., Aim: To assess lung function by spirometry in relation to the clinical characteristics of A-T patients followed up at the Israeli Ataxia Telangiectasia National Clinic., Patients and Methods: Medical and spirometry data were collected from 27 A-T patients during 2004-2007. Laboratory, nutritional condition, mode of treatment, pulmonary status, and malignancies were assessed. The spirometry values FVC, FEV(1), FEV(0.5), FEF(25-75), PEF and time rise to peak flow were analyzed individually and values were compared to those of healthy age-matched children., Results: Eleven patients (40.7%) were found to suffer from asthma according to clinical symptoms and response to bronchodilators. We found significant reduction in FEV(1) and FEV(0.5) (z-scores: -0.84 + or - 0.7 SD, -0.7 + or - 0.6 SD; P = 0.0014 and P = 0.003, respectively), in relation to healthy predicted values. FEF(25-75) was significantly lower than that in healthy children in 5 of 11 asthmatic patients. All 27 patients showed higher than healthy FEV(1)/FVC and FEV(0.5)/FVC ratios (z-scores 0.68 + or - 0.99 SD, P < 0.0015, and 2.12 + or - 1.50 SD, P < 0.0015, respectively). The rise time to peak flow was three-fold longer than that of healthy children., Conclusion: Obstructive lung disease is common among A-T patients. Maximal peak flow reduction and prolonged rise time to peak flow may be the first signs of pulmonary involvement in these patients. Early treatment with anti-asthma therapy, bronchodilators, and steroids, may prevent further pulmonary deterioration and improve the prognosis of A-T patients.