Susceptibility to Infections in Ataxia Telangiectasia
Condition: Ataxia Telangiectasia; Infections; Immunodeficiency; Lung Disease
MeSH terms: Infections; Communicable Diseases; Lung Diseases; Ataxia; Cerebellar Ataxia; Ataxia Telangiectasia; Telangiectasis
Study type: Interventional

Summary: 
      Death in Ataxia telangiectasia (A-T) is usually due to cancer or chronic lung failure around
      20 years of age. Despite low lymphocyte counts (CD3, CD4, CD8 and CD19), IgA and IgG subclass
      deficiency opportunistic and acute severe respiratory infections are rare. The prevailing
      wisdom is that an immunoglobulin replacement therapy is not necessary in most of the
      patients. However no placebo controlled trials have been performed so far. The aim of this
      trial was to investigate the prevalence of mild and severe respiratory infections and / or
      chronic cough in classical A-T patients compared to healthy controls.
    

Detailed description: 
      Ataxia telangiectasia is an autosomal recessive multisystem disorder which is characterized
      by a progressive ataxia, conjunctival telangiectasia, a humoral and cellular
      immunodeficiency, an increased radiosensitivity and an increased risk for cancer (Boder E,
      Pediatrics, 1957). Most patients die in their 2nd or 3rd decade of life due to a respiratory
      failure caused by progressive (interstitial) lung disease or due to malignancies (Schroeder
      SA, Pediatr Pulmonol, 2010). In 1995 the sequence of the mutated AT gene (ATM) on chromosome
      11q22-23 was identified. Main problems besides the progressive neurodegeneration are
      recurrent infections of upper and lower respiratory tract and a growth retardation and
      malnutrition. These problems are caused by a mutation in the ATM gene on chromosome 11, which
      encodes for a protein with several key functions in control of cell cycle and apoptosis
      (Savitsky K et al., Hum Mol Gen, 1995). Several works already showed that patients with AT
      have a variable immunodeficiency which is characterized by low lymphocyte counts, a lack of
      Immunoglobulin A (IgA), Immunoglobulin G subclasses (IgG2 and 4) and specific pneumococcal
      antibodies (Schubert R, Clin Exp Immunol, 2002). The course of disease is dependent on the AT
      mutation respectively the residual kinase activity of ATM which is found in about 10% of A-T
      patients. These patients are described as 'variant ATs´ and have a better prognosis regarding
      immunodeficiency, susceptibility to infections and a possible growth retardation and
      malnutrition (Verhagen M, Hum Mutat, 2012). Despite the evidence for a humoral
      immunodeficiency a treatment with polyvalent immunoglobulins (IgG) is not practiced in
      generally. In the 'Clinical Workshop on Ataxia Teleangiectasia´, that took place in Frankfurt
      in January 2011, the investigators found out that the percentage of A-T patient, that are
      supplemented with immunoglobulins was only 10% to 60% depending on the different clinical
      centres.The Goethe University Childrens Hospital in Frankfurt, the biggest A-T centre in
      Germany, takes care for more than 40 A-T patients. At the moment about 15% of these patients
      are treated with immunoglobulins. Some observations show that the progress of the chronic
      lung disease cannot be prevented the usage of immunoglobulins. By now it´s not clear in what
      way patients suffer from an increased susceptibility to infections and if a substitution with
      immunoglobulins is needed. The aim of this trial is to investigate the incidence, intensity
      and duration of infections in patients with A-T compared to age matched healthy controls.
    

Intervention name(s): Blood collection; Lung function measurement; Symptom diary
Intervention type(s): Procedure; Procedure; Behavioral
Intervention description(s): In all patients with Ataxia telangiectasia blood was collected at each visit date to determine blood count, lymphocyte subpopulation count and immunoglobulin levels in serum (IgA, IgG, IgM, IgE), as well as alpha feto protein (AFP).; In all patients - Ataxia telangiectasia and healthy controls - a lung function measurement was done to determine vital capacity (VC), forced expiratory volume in 1 second (FEV1), peak expiratory flow (PEF) and Tiffenau index.; All patients - Ataxia telangiectasia and healthy controls - were requested to keep a symptom diary for the months September to March of the years 2012/2013 and 2013/2014 to determine days with symptoms as coughing during day and night, cold and fever, as well missing days at kindergarten/school/work, intake of medication (especially antibiotic treatment) and hospitalisations.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care