Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

13 children with ataxia-telangiectasia were followed for 6 years. Unlike previously reported cases, these patients had progressive, debilitating neurological disease and slight pulmonary or infectious symptoms. Immunological dysfunction was variable and endocrinological defects were absent. Oculomotor findings, alpha-fetoprotein levels, and the incidence of chromosomal breakage were the most consistent parameters in the diagnosis of the condition. This disease should be considered in any patient with chronic ataxia, regardless of immunological findings or whether he has a history of infections.
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PMID:Diagnostic considerations in ataxia-telangiectasia. 9 14

Seventy individuals with ataxia telangiectasia were studied: 29 females and 41 males with an age range of 2 to 42 years. The majority (43/68) presented by 3 years of age with truncal ataxia. All had progressive, handicapping neurological symptoms exhibiting ataxia (70/70), ocular motor apraxia (70/70), an impassive face (70/70), dysarthria (70/70), chorea (68/70), dystonia (55/70) and peripheral neuropathy (50/70). Clinical immune deficiency was present in 43 of 70 patients. Ocular telangiectasia were seen in all but one case and excessive thinness in 54 of 70. The mean age of loss of walking was 10 years and of writing 8 years. All 60 tested showed increased sensitivity to ionizing irradiation, 43 of 48 had an elevated alpha-fetoprotein level and 14 of 21 had an immunoglobulin deficiency. Although there was a marked variation in disease findings sibs were always similar. The heterogeneity seen seems at odds with the unilocus linkage of ataxia telangiectasia to 11q23.
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PMID:Ataxia telangiectasia in the British Isles: the clinical and laboratory features of 70 affected individuals. 137 28

Ataxia-telangiectasia (A-T) is a progressive autosomal recessive disease featuring neurodegeneration, immunodeficiency, chromosomal instability, radiation sensitivity and a highly increased proneness to cancer. A-T is ethnically widespread and genetically heterogeneous, as indicated by the existence of four complementation groups in this disease. Several "A-T-like" genetic diseases share various clinical and cellular characteristics with A-T. By using linkage analysis to study North American and Turkish A-T families, the ATA (A-T, complementation group A) gene has been mapped to chromosome 11q23. A number of Israeli Arab A-T patients coming from large, highly inbred families were assigned to group A. In one of these families, an additional autosomal recessive disease was identified, characterized by ataxia, hypotonia, microcephaly and bilateral congenital cataracts. In two patients with this syndrome, normal levels of serum immunoglobulins and alpha-fetoprotein, chromosomal stability in peripheral blood lymphocytes and skin fibroblasts, and normal cellular response to treatments with X-rays and the radiomimetic drug neocarzinostatin indicated that this disease does not share, with A-T, any additional features other than ataxia. These tests also showed that another patient in this family, who is also mentally retarded, is affected with both disorders. This conclusion was further supported by linkage analysis with 11q23 markers. Lod scores between A-T and these markers, cumulated over three large Arab families, were significant and confirmed the localization of the ATA gene to 11q23. However, another Druze family unassigned to a specific complementation group, showed several recombinants between A-T and the same markers, leaving the localization of the A-T gene in this family open.
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PMID:Ataxia-telangiectasia: linkage analysis in highly inbred Arab and Druze families and differentiation from an ataxia-microcephaly-cataract syndrome. 155 65

This report describes twin girls with typical features of ataxia-telangiectasia, including increased alpha-fetoprotein, radio-resistant DNA synthesis, characteristic chromosome abnormality, and immunodeficiency. They have, in addition, microcephaly and mental retardation. Complementation studies were performed utilizing Sendai virus--mediated fusion of fibroblast cell lines. Complementation was observed with patients in ataxia-telangiectasia complementation groups A, C, and E but not with the cell line from a patient with the Nijmegen breakage syndrome, in which patients have microcephaly, radio-resistant DNA synthesis, chromosome aberrations, and immunodeficiency but lack ataxia and telangiectasia. These data suggest that the Nijmegen breakage syndrome and the patients described here are not genetically distinct entities but form a spectrum of one disorder.
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PMID:ATFresno: a phenotype linking ataxia-telangiectasia with the Nijmegen breakage syndrome. 249 Nov 81

Sixty-eight human fibroblast cell strains were assayed for radioresistant DNA synthesis (RDS), which is defined here as the absence of a steep component of inhibition of DNA synthesis in a dose-response curve when rate of DNA synthesis is plotted against radiation doses from 0 to 20 Gy or more. Twenty-seven strains from patients who were previously diagnosed to have ataxia-telangiectasia (AT) were positive for this feature. Among the cell strains that did not show RDS were two from AT obligate heterozygotes (i.e., the parents of AT patients), two from patients with Alzheimer disease, two from patients with Friedreich ataxia, one from a patient with Bloom syndrome, one from a patient with Down syndrome, and six from patients with various immunodeficiencies. Four strains demonstrated RDS that was less pronounced than in most AT cells: one was from a patient with Nijmegen breakage syndrome, one was from a patient without ataxia but with choreiform movement disorder, telangiectasia, and elevated concentrations of alpha-fetoprotein in the blood, and two were from AT patients. RDS therefore is not a necessary trait of human genetic diseases that involve radiosensitivity or immunodeficiency. Although recent reports suggest that some AT patients do not exhibit RDS, we found RDS in all the AT cells we tested.
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PMID:Radioresistant DNA synthesis and human genetic diseases. 272 85

We report on five independent families with a chromosome instability disorder that earlier had been called the Nijmegen breakage syndrome (NBS). These families, two from the Netherlands and three from Czechoslovakia, had a total of eight patients, five of whom are still alive. The main clinical manifestations were microcephaly, short stature, a "bird-like" face, immunological defects involving both the humoral and cellular system. In four of the five living patients it has been possible to study the chromosomes of cultured lymphocytes. The basic karyotype in these patients were normal, but in 17% to 35% of the metaphases rearrangements were found, preferentially involving chromosomes 7 and/or 14 at the sites 7p13, 7q34, and 14q11. The chromosomes of all five living patients were very sensitive to ionizing radiation. In addition, the DNA synthesis in their cultured lymphocytes and fibroblasts was more resistant to X-rays than in cells from controls. The NBS shares a number of important features with ataxia telangiectasia (AT). Both syndromes are characterized by the occurrence of typical rearrangements of chromosomes 7 and/or 14, cellular and chromosomal hypersensitivity to X-irradiation, radioresistance of DNA replication and immunodeficiency. However, there are also obvious differences: NBS patients have microcephaly but neither ataxia nor telangiectasia, and in contrast to the situation in AT the alpha-fetoprotein level in their serum is normal.
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PMID:Further delineation of the Nijmegen breakage syndrome. 278 40

We report 14 patients with a slowly progressive syndrome featuring ataxia, choreoathetosis, and ocular motor apraxia in both the horizontal and vertical planes. Although the neurological signs were indistinguishable from those of ataxia-telangiectasia, the onset tended to be later and none of the patients had evidence of multisystemic involvement. Specifically, there was no tendency to frequent infections, and immunoglobulins, alpha-fetoprotein, T- and B-lymphocyte markers, and chromosomes 7 and 14 were normal in all tested patients. The simultaneous absence of telangiectasias and of other nonneurological manifestations made ataxia-telangiectasia an unlikely diagnosis. We suggest that these patients suffer from an unusual type of spinocerebellar degeneration. This syndrome has been observed in different populations from three continents, with a genetic pattern suggesting recessive autosomal inheritance.
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PMID:Ataxia-ocular motor apraxia: a syndrome mimicking ataxia-telangiectasia. 323 52

As a part of studies on cell-mediated immune (CMI) responses of immunocompromised, Epstein-Barr virus (EBV)-infected patients who can or cannot restrict the proliferation of EBV-transformed B cells, we have studied 16 Turkish patients with ataxia-telangectasia (AT). Fifteen were EBV seropositive; one was seronegative. Among the seropositives, eight had no or only low anti-EBV-determined nuclear antigen (EBNA) antibody titers, while seven had normal anti-EBNA levels. EBV-seropositive and -seronegative healthy Turkish children were used as controls. We have particularly asked the question whether low EBNA antibody titers can be correlated with the level of EBV-specific and -nonspecific cell-mediated immunity. Non-EBV-specific tests included cell count, phenotypical characterization with monoclonal antibodies, assessment of natural killer (NK)-cell activity, and ability to suppress mitogen-induced immunoglobulin production. Two EBV-specific CMI tests were used: outgrowth inhibition (OI) and leukocyte migration inhibition (LMI). The majority of the patients of the low-EBNA antibody group was IgA deficient and had high levels of alpha-fetoprotein (a-FP). Cells reacting with OKT8 monoclonal antibody predominated in both AT patient groups. In contrast, the suppressor activity was present in only a few patients and NK and interferon-activated killing (IAK) activities were normal. EBV-specific cell-mediated responses were defective in seven of eight patients in the low-anti-EBNA group and five of seven patients in the group with normal anti-EBNA titers. It is concluded that AT patients are often defective in their EBV-specific cell-mediated immune responses and with regard to their EBNA antibody levels. These defects are associated with a predominance of T cells reacting with OKT8 monoclonal antibody.
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PMID:Epstein-Barr virus (EBV)-specific cell-mediated and humoral immune responses in ataxia-telangectasia patients. 609 13

Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by telangiectasia, progressive ataxia, sinopulmonary infections and a combined immunodeficiency (usually consisting of IgA deficiency, IgE deficiency, IgG2 and IgG4 deficiency and a disturbed T cell immunity). The alpha-fetoprotein level is elevated. Cytogenetic studies reveal a very specific chromosome instability with multiple chromosome 7 and/or 14 rearrangements (preferential breakpoints 14q32, 14q12, 7q35 and 7p12). X-ray hypersensitivity is one of the hallmarks of the disease. Nijmegen Breakage Syndrome (NBS), an autosomal recessive disorder with some features of AT, was first reported in 1981. At this moment at least 19 patients have been recognized. Clinical symptoms are microcephaly from birth, a peculiar face, growth retardation, repeated respiratory tract infections and renal abnormalities. Immunological, cytogenetic and cell-biological findings in NBS are identical to AT. However, alpha-fetoprotein levels are not increased. A tendency toward malignancy has been demonstrated in both syndromes. Recently, we encountered three patients with variants of these syndromes.
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PMID:Variants of Nijmegen breakage syndrome and ataxia telangiectasia. 751 25

Seventeen cases of ataxia telangiectasia (AT) were diagnosed over a period of 10 years. The children affected by AT were aged about 7 years and they were preferentially males (67%). The principal clinical aspects were: cerebellous ataxia (98%), recurrent ENT infections (86%) and ocular telangiectasia (96%). We also showed an immune function defect mainly concerning IgA, which was associated with cellular immunity abnormalities (lymphopenia, negative hypersensitivity reactions). The alpha-fetoprotein (AFP) values were high and increased in proportion to the severity of the neurologic manifestations. Thus, this parameter could be used as a diagnostic index of the illness and could be a precious indicator for the management and the evolution of these patients.
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PMID:[Ataxia telangiectasia. Clinical and biological study in 17 cases]. 752 81


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