Diabetes in Patients With Ataxia Telangiectasia: A National Cohort Study

Donath, H; Heß, Ursula; Kieslich, Matthias; Theis, Marius; Ohlenschläger, Ute; Schubert, Ralf; Woelke, Sandra; Zielen, Stefan

doi:10.3389/fped.2020.00317

Cited by 20 publications

(13 citation statements)

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“…Ataxia telangiectasia (A-T) is a pleiotropic and devastating human autosomal recessive disorder with genetic instability. Prominent features are cerebellar degeneration, oculocutaneous telangiectasia, immunodeficiency, cancer predisposition, and endocrinological abnormalities, such as insulin resistance, diabetes, and growth retardation [ 1 , 2 ]. Recurrent infections and aspiration contribute to lung disease and favor the development of bronchiectasis and respiratory failure [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Neurofilament Light Chain Is a Biomarker of Neurodegeneration in Ataxia Telangiectasia

et al. 2021

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Ataxia telangiectasia (A-T) is a progressive and life-limiting disease associated with cerebellar ataxia due to progressive cerebellar degeneration. In addition to ataxia, which is described in detail, the presence of chorea, dystonia, oculomotor apraxia, athetosis, parkinsonism, and myoclonia are typical manifestations of the disease. The study aimed to evaluate the specificity and sensitivity of neurofilament light chain (NfL) as a biomarker of neurodegeneration in relation to SARA score. In this prospective trial, one visit of 42 A-T patients aged 1.3–25.6 years (mean 11.6 ± 7.3 years) was performed, in which NfL was determined from serum by ELISA. Additionally, a neurological examination of the patients was performed. Blood was collected from 19 healthy volunteers ≥ 12 years of age. We found significantly increased levels of NfL in patients with A-T compared to healthy controls (21.5 ± 3.6 pg/mL vs. 9.3 ± 0.49 pg/mL, p ≤ 0.01). There was a significant correlation of NfL with age, AFP, and SARA. NfL is a new potential progression biomarker in blood for neurodegeneration in A-T which increases with age.

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Section: Introductionmentioning

confidence: 99%

Neurofilament Light Chain Is a Biomarker of Neurodegeneration in Ataxia Telangiectasia

et al. 2021

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“…Individuals with A-T have been found to have cholesterol profiles associated with a higher risk for cardiovascular disease, 24 diabetes with insulin resistance, 25 and steatohepatitis. 26 , 27 These findings suggest that ATM dysregulation is associated with the development of metabolic syndrome.…”

Section: Cardiovascular and Liver And Metabolic Conditionsmentioning

confidence: 99%

Multidisciplinary Management of Ataxia Telangiectasia: Current Perspectives

McGrath‐Morrow¹,

Rothblum-Oviatt²,

Wright³

et al. 2021

JMDH

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Ataxia telangiectasia (A-T) is a rare autosomal recessive disease caused by mutations in the ataxia telangiectasia mutated ( ATM ) gene. In the absence of a family history, the diagnosis of A-T is usually not made until the child is older and symptomatic. Classic A-T is characterized by a constellation of clinical symptoms including progressive ataxia, oculocutaneous telangiectasias and sinopulmonary disease and is usually associated with absence of ATM protein. Other laboratory features associated with A-T include elevated serum levels of alpha-fetoprotein (AFP) and increased chromosomal breakage with in vitro exposure to ionizing radiation. Sinopulmonary symptoms can occur to varying degrees across the lifespan. Some children will also have hypogammaglobulinemia and impaired antibody responses requiring supplemental gamma globulin. People with hypomorphic ATM mutations are often considered to have mild A-T with onset of ataxia and neurological progression occurring later in life with less impairment of the immune system. The risk of malignancy, however, is significantly increased in people with either classic or mild A-T. While hematological malignancies are most common in the first two decades of life, solid organ malignancies become increasingly common during young adulthood. Deterioration of neurologic function with age is associated with dysphagia with aspiration, growth faltering, loss of ambulation and decline in pulmonary function, morbidities that contribute to shortened life expectancy and decreased quality of life. Premature death is often due to malignancies or chronic respiratory insufficiency. A-T is currently managed with supportive care and symptomatic treatment. Current clinical trials, however, represent progress and hope towards disease-modifying therapies for A-T.

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“…Of note, solid tumors mainly present in adulthood, with majority being breast, liver, gastric, thyroid, and esophageal carcinomas Appendix 2,4,7 . Finally, diabetes mellitus and particularly the raised AFP of unknown cause were also consistent with A‐T 19‐21 …”

Section: Discussionmentioning

confidence: 79%