Body Composition and Hormonal Status in Ataxia Telangiectasia
Study Details
Study Description
Brief Summary
Ataxia telangiectasia (A-T) is a rare devastating human recessive disorder characterized by progressive cerebellar ataxia, immunodeficiency, chromosomal instability, and cancer susceptibility. In addition to that, a high percentage of patients show dystrophy, growth retardation and poor weight gain. Nevertheless, there are only a few studies assessing this problem. Aim of the present proposal is to investigate the exact body composition, manual muscle strength and hormonal status in patients with A-T compared to healthy controls matched for gender and age. A pelvic sonography in females was performed in order to evaluate the sexual maturity of their inner genitalia. Tanner score was determined to define the physical development. Every subject received a nutritional diary to review its calorie intake and the quality of diet. The investigators expect that the A-T cohort shows an altered body composition, impaired muscle strength, changed hormonal status concerning the sexual hormones and a delayed physical development compared to healthy controls.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Detailed Description
Ataxia telangiectasia (A-T) is a devastating human recessive disorder characterized by progressive cerebellar ataxia, immunodeficiency, chromosomal instability, and cancer susceptibility. In addition to that, a high percentage of patients show dystrophy, growth retardation and poor weight gain. There are only a few studies assessing this problem and the exact variations concerning body composition, muscle strength and hormonal status are widely unknown.
Major factors may be responsible for altered body composition:
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Immunodeficiency and chronic disease are important influences on growth and physical development. The constantly catabolic situation of A-T patients has a major impact on dystrophy.
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Due to the progressive cerebellar ataxia most of the patients are bound to wheelchair so that their muscle mass is decreased
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Impaired muscle strength is related to apraxia, dystonia, contractures and dyskinesia.
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Low levels of growth hormones (GH). Extracerebellar MRI - lesions in A-T go along with deficiency of the GH axis thus causing nanism.
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Delayed puberty and physical development suggest an abnormal metabolism in muscle cells
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There are autopsy reports informing about reduced mass of the adrenal cortex that may be reflected in a lower hormone release of steroid hormones.
The aim of the proposal is to explore the exact body composition, the manual muscle strength, the hormonal status in patients with A-T compared to healthy subjects matched for sex and age. One study visit is performed in all A-T patients and healthy subjects:
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To evaluate weight and length of all subjects
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To analyze the exact structure of single body compartments such as the lean mass, the water compartment or the fat compartment using bioelectrical impedance analysis
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To determine the subcutaneous fat fold thickness using calipometry
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To investigate the nourishment habits and diet detected by nutritional diary
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To analyze the manual muscle strength with a hand dynamometer
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To determine the physical development in the A-T cohort by Tanner scores
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To evaluate stage of sexual development and puberty in female A-T patients by ultrasonic of the inner genitalia
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To get a detailed hormonal status including thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), GH, cortisol, DHEAS, estradiol, testosterone, progesterone, insulin like growth factor-binding protein 3 (IGF-BP3), etc in serum blood
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Ataxia telangiectasia 26 patients with clinically and/or genetically diagnosed Ataxia telangiectasia will be examined with bioelectrical impedance analysis (BIA), muscle force measurement, calipometry and get a blood draw |
Procedure: bioelectrical impedance analysis
electrophysical measurement that allows to determine the exact composition of single body compartments by producing a magnetic field and detecting the potential difference through the body
Procedure: blood draw
blood samples are taken at 8 am in order to pay attention to the circadian rhythmicity to get a detailed hormonal status
|
| Active Comparator: Healthy subjects 26 age and sex matched subjects without any chronic disease or hormone displacement will be examined with bioelectrical impedance analysis (BIA), muscle force measurement, calipometry and get a blood draw |
Procedure: bioelectrical impedance analysis
electrophysical measurement that allows to determine the exact composition of single body compartments by producing a magnetic field and detecting the potential difference through the body
Procedure: blood draw
blood samples are taken at 8 am in order to pay attention to the circadian rhythmicity to get a detailed hormonal status
|
Outcome Measures
Primary Outcome Measures
- Body mass index [12 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
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aim group: clinically and/or genetically diagnosed A-T
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control group: age and sex matched healthy subjects
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age 2-45 years
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written informed consent
Exclusion Criteria:
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age < 2 or > 45 years
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other diseases with influence on the immunosystem (i.e. diabetes mellitus, malignoma, dialysis-dependent renal failure)
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current medication with hormones
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Johann Wolfgang Goethe University Hospital
Investigators
- Principal Investigator: Stefan Zielen, Prof. Dr., University Childrens´ Hospital Frankfurt
Study Documents (Full-Text)
None provided.More Information
Publications
- Baldin AD, Fabbri T, Siviero-Miachon AA, Spinola-Castro AM, de Lemos-Marini SH, Baptista MT, D'Souza-Li LF, Maciel-Guerra AT, Guerra-Junior G. Growth hormone effect on body composition in Turner syndrome. Endocrine. 2011 Dec;40(3):486-91. doi: 10.1007/s12020-011-9504-z. Epub 2011 Jul 1.
- Cosentino C, Grieco D, Costanzo V. ATM activates the pentose phosphate pathway promoting anti-oxidant defence and DNA repair. EMBO J. 2011 Feb 2;30(3):546-55. doi: 10.1038/emboj.2010.330. Epub 2010 Dec 14.
- DUNN HG, MEUWISSEN H, LIVINGSTONE CS, PUMP KK. ATAXIA-TELANGIECTASIA. Can Med Assoc J. 1964 Nov 21;91:1106-18.
- Kieslich M, Hoche F, Reichenbach J, Weidauer S, Porto L, Vlaho S, Schubert R, Zielen S. Extracerebellar MRI-lesions in ataxia telangiectasia go along with deficiency of the GH/IGF-1 axis, markedly reduced body weight, high ataxia scores and advanced age. Cerebellum. 2010 Jun;9(2):190-7. doi: 10.1007/s12311-009-0138-0.
- Menotta M, Biagiotti S, Bianchi M, Chessa L, Magnani M. Dexamethasone partially rescues ataxia telangiectasia-mutated (ATM) deficiency in ataxia telangiectasia by promoting a shortened protein variant retaining kinase activity. J Biol Chem. 2012 Nov 30;287(49):41352-63. doi: 10.1074/jbc.M112.344473. Epub 2012 Oct 10.
- Schubert R, Reichenbach J, Zielen S. Growth factor deficiency in patients with ataxia telangiectasia. Clin Exp Immunol. 2005 Jun;140(3):517-9.
- Voss S, Pietzner J, Hoche F, Taylor AM, Last JI, Schubert R, Zielen S. Growth retardation and growth hormone deficiency in patients with Ataxia telangiectasia. Growth Factors. 2014 Jun;32(3-4):123-9. doi: 10.3109/08977194.2014.939805.
- BIA_AT2014