Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Determinations of IgG subclasses were made by electroimmunoassay and crossed immunoelectrophoresis, and Gm markers were typed in sera from seventeen patients with well-defined immunodeficiency diseases. Certain IgG subclass and Gm patterns were recognized in various diseases: IgG2 deficiency and homozygosity of Gm (4,5) in the cartilage-hair-hypoplasia syndrome, in the ataxia telangiectasia syndrome and in selective IgG subclass deficiency; and IgG3 deficiency and homozygosity of Gm(1,-5) in the Wiskott-Aldrich syndrome. The findings suggest a common structural or regulator gene defect in some immunodeficiency diseases. In IgA deficiencies, the levels of IgG1 were raised. In patients with IgG subclass deficiencies there was sometimes a compensatory increase of the remaining IgG subclasses, with a preponderance of IgG1 and IgG3. The increased Ig1 showed restricted heterogeneity with only an increase of the electrophoretically cathodal part. This part contained both kappa and lambda chaings. IgG subclass deficiency indicates treatment with gammaglobulin even if the serum levels of IgG are normal or increased.
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PMID:Quantitative and qualitative investigations of serum IgG subclasses in immunodeficiency diseases. 46 57

Patients with primary or secondary IgG subclass deficiencies suffer from infections due to encapsulated microorganisms such as H influenzae and pneumococci. In addition to relapsing infections, some patients with primary subclass deficiencies may have autoimmune disorders. The best characterized defect in IgG2 deficiency, either isolated or combined with IgG4 deficiency. It is frequently associated with IgA deficiency or with ataxia telangiectasia. IgG1 deficiency occurs mostly in combination with disturbances of other immunoglobulin isotypes, and probably represents a form of common variable immune deficiency. Decreased IgG3 levels were reported in association with lung dysfunction and viral diseases. Except in IgG1 deficiency, total IgG serum levels in primary as well as secondary IgG subclass deficiency states may be normal or even increased. It is assumed that IgG subclass deficiencies represent an indicator of more basic immunologic abnormalities. There is evidence that antibody defects correlate better with the clinical symptoms than the total serum IgG subclass concentrations. In patients with severe recurrent infections and IgG subclass deficiency, intravenous immunoglobulin treatment at dosages of 0.3 to 0.4 g/kg body weight every 3-4 weeks is indicated.
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PMID:Clinical relevance of IgG subclass deficiencies. 821 74

Ataxia telangiectasia (A-T) is a rare autosomal recessive multisystem disease. The diagnosis of A-T is based on the typical clinical picture: ataxia and telangiectasia. However, an increase in (alpha-fetoprotein (AFP) level and the identification of the A-T mutated gene (ATM) assist in an early diagnosis. Here we report two cases of A-T diagnosed in our hospital (case 1: a 7-year-old boy; case 2: an 8-year-old girl). Both of these patients had typical clinical pictures of ataxia and telangiectasia, AFP was also increased (case 1:471.2 ng/dL; case 2: 196 ng/dL). T-cell dysfunction was noted in both patients. Case 1 had IgG2 deficiency and case 2 had IgA, IgG2 and IgG3 deficiency. Case 2 developed malignant lymphoma at 9 years of age and died of pneumonia with respiratory failure at 10 years of age. Because of rhe rarity of A-T in Taiwan, we report two cases to help pediatricians make an early diagnosis of A-T if they have a patient with progressive ataxia and oculocutaneous telangiectasia.
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PMID:Ataxia telangiectasia: report of two cases. 1132 Nov 31

Selective IgA deficiency is the most common primary immunodeficiency, with a prevalence of approximately 1/600 in whites. Most subjects are asymptomatic but some may suffer from frequent respiratory and gastrointestinal infections. Patients who suffer from frequent infections usually have a defect in antibody responses toward polysaccharides, which is often associated with IgG2 deficiency. Genetic predisposition to develop IgA deficiency has been shown to be linked to at least one locus on 6p21. Some IgA-deficient patients are also prone to develop more severe immunodeficiency called common variable immunodeficiency, which is associated with decreased IgG and sometimes IgM production as well as partial T-cell defect. In a few cases, IgA deficiency may reveal a severe disease such as ataxia-telangiectasia. Selective IgA deficiency contraindicates immunoglobulin administration. Only the minority of IgA-deficient patients who develop severe or frequent infections in association with IgG2 deficiency or impaired antibody response are candidates for prophylactic intravenous immunoglobulin substitution. Immunoglobulin preparations containing particularly low amounts of IgA are required to avoid adverse effects related to anti-IgA alloantibodies.
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PMID:[IgA deficiency]. 1144 86

Eleven Norwegian patients (aged 2-33 years, seven males and four females) with Ataxia-telangiectasia (A-T) and their parents were investigated. Five of the patients were homozygous for the same ATM mutation, 3245delATCinsTGAT, a Norwegian founder mutation. They had the lowest IgG2 levels; mean (95% confidence interval) 0.23 (0.05-0.41) g/l versus 0.91 (0.58-1.26) g/l in the other patients (P = 0.002). Among the 11 A-T patients, six had IgG2 deficiency, six had IgA deficiency (three in combination with IgG2 deficiency) and seven had low/undetectable IgE values. All patients had very low levels of antibodies to Streptococcus pneumoniae 0.9 (0.4-1.4) U/ml, while normal levels were found in their parents 11.1 (8.7-13.4) U/ml (P < 0.001). A positive linear relationship between pneumococcal antibodies and IgG2 (r = 0.85, P = 0.001) was found in the patients. Six of 11 had diphtheria antibodies and 7 of 11 tetanus antibodies after childhood vaccinations, while 4 of 7 Hemophilus influenzae type b (Hib) vaccinated patients had protective antibodies. Ten patients had low B cell (CD19+) counts, while six had low T cell (CD3+) counts. Of the T cell subpopulations, 11 had low CD4+ cell counts, six had reduced CD8+ cell counts, and four had an increased portion of double negative (CD3+/CD4-/CD8-) gamma delta T cells. Of the 22 parents (aged 23-64 years) 12 were heterozygous for the ATM founder mutation. Abnormalities in immunoglobulin levels and/or lymphocyte subpopulations were also observed in these carriers, with no correlation to a special ATM genotype.
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PMID:The impact of an early truncating founder ATM mutation on immunoglobulins, specific antibodies and lymphocyte populations in ataxia-telangiectasia patients and their parents. 1519 60

We report four patients with ataxia-telangiectasia syndrome that presented varied neurologic evolution. Three patients initially presented neurologic alterations of slow progression, evolving to late immunocompromised conditions. The fourth patient presented, from symptom onset, immune and neurologic debilitation, that were both severe and of fast progression. The chronological sequence of the most commonly observed immunocompromised conditions were in our patients, in ascending order, IgA deficiency, IgG2 deficiency and the neutrophil phagocytosis stage and common variable immunodeficiency. The first two reports are of sisters in whom the diagnosis was done between the ages of three and six years, having ocular apraxia, cerebellar ataxia and telangiectasia. Slow progression of neurologic debilitation was observed, without presentation of intermittent infections. The patients began presenting accentuated immunocompromised conditions at the ages of 14 and 17 years, dying at the ages of 16 and 20 years, respectively, due to severe infections that were resistant to treatment. The diagnosis of the third case was established when the patient was two years old, presenting ataxia and telangiectasia. Syndrome progression was slow, presenting at the age of eight years more accentuated neurologic disorders and IgA deficiency. The fourth case presented significant neurologic compromise at the age of five, simultaneous to IgA and IgG2 deficiency, and repeating pneumonias and sinusitis. At this time, intravenous gammaglobulin reposition was done. The neurologic and immune disorders progressed rapidly, and at the age of eight presented the inability to walk. At this time inversion of the CD4/CD8 ration was verified through laboratory tests.
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PMID:Different clinical and laboratory evolutions in ataxia-telangiectasia syndrome: report of four cases. 1604 57

Some primary immunodeficiencies (PIDs) express low serum levels of antibodies. The constant heavy G chain (IGHG) genes, also representing Fc domains of gamma 3, gamma 1 and gamma 2 on chromosome 14q32.3, genotyped by the alternative IgG subclass allotypes, found in four fixed IGHG haplotypes, designating four B cell variants, were identified by a competitive ELISA and double immunodiffusion. IGHG genes were hypothesized to contribute to the development of PIDs. From 235 Caucasian patients, the homozygous IGHG *bf-n/*bf-n diplotype (B*(bf-n)/B*(bf-n) cells) dominated significantly in 43 IgG2 deficiency (OR 6.0), 32 common variable immunodeficiency (OR 4.6) and 22 Ataxia telangiectasia (OR 3.0) and the IGHG*ga-n/*ga-n diplotype (B*(ga-n)/B*(ga-n) cells) dominated in 53 IgG3 deficiency (OR 10.6) and 21 Wiscott-Aldrich syndrome (OR 4.1). 62 IgA deficiency patients were dominated by both diplotypes (OR 2.3 and OR 2.8 respectively). Restricted IGHG genes, restricted IgG allotypes (Fc domains) and restricted B cells are significant in PIDs for diagnosis, treatment and pathogenetic mechanisms.
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PMID:Restricted immunoglobulin constant heavy G chain genes in primary immunodeficiencies. 1850 79