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Keywords
- ataxia telangiectasia (2)
- malignancy (2)
- primary immunodeficiency (2)
- Ataxia telangiectasia (1)
- Ataxia-telangiectasia (1)
- HbA1c (1)
- OGTT (1)
- ataxia score (1)
- cancer surveillance (1)
- combined immunodeficiency (1)
- Diabetes in patients with ataxia telangiectasia: A national cohort study (2020)
- Background: Ataxia telangiectasia (A-T) is a rare autosomal-recessive multisystem disorder characterized by pronounced cerebellar ataxia, telangiectasia, cancer predisposition and altered body composition. In addition, evidence is rising for endocrine dysfunction. Objectives: To determine the evolution of diabetes and its prevalence in a larger A-T cohort. Methods: A retrospective analysis of the patient charts of 39 subjects from the Frankfurt A-T cohort was performed between August 2002 and 2018 concerning HbA1c and oral glucose tolerance (OGTT). The median follow-up period was 4 years (1–16 years). In addition, in 31 A-T patients aged 1 to 38 years HbA1c and fasting glucose were studied prospectively from 2018 to 2019. Results: In the retrospective analysis, we could demonstrate a longitudinal increase of HbA1c. The prospective analysis showed a significant increase of HbA1c and fasting glucose with age (r = 0.79, p ≤ 0.0001). OGTT has a good sensitivity for insulin resistance screening, whereas HbA1c can be used to evaluate individual courses and therapy response. Seven out of 39 (17.9%) patients suffered from diabetes. Metformin did not always lead to sufficient diabetes control; one patient was treated successfully with repaglinide. Conclusion: Diabetes is a common finding in older A-T patients and often starts in puberty. Our data clearly demonstrate the need for an annual diabetes screening in patients > 12 years.
- Progressive liver disease in patients with ataxia telangiectasia (2019)
- Ataxia telangiectasia (A-T) is a devastating multi-system disorder characterized by progressive cerebellar ataxia, immunodeficiency, genetic instability, premature aging and growth retardation. Due to better care the patients get older than in the past and new disease entities like disturbed glucose tolerance and liver disease emerge. The objective of the present investigation is to determine the evolution of liver disease and its relation to age and neurological deterioration. The study included 67 patients aged 1 to 38 years with classical A-T. At least two measurements of liver enzymes were performed within a minimum interval of 6 months in 56 patients. The median follow-up period was 4 years (1–16 years). A total of 316 liver enzyme measurements were performed. For analysis, patients were divided into two age groups (Group 1: <12 years; group 2: ≥12 years). In addition, ultrasound of the liver and Klockgether Ataxia Score (KAS) were analyzed. We found significantly higher levels of alpha-fetoprotein (AFP) (226,8 ± 20.87 ng/ml vs. 565,1 ± 24.3 ng/ml, p < 0.0001), and liver enzymes like ALT (23.52 ± 0.77 IU/L vs. 87.83 ± 5.31 IU/L, p < 0.0001) in patients in group 2. In addition, we could show a significant correlation between age and AFP, GGT, and KAS. Ultrasound revealed hepatic steatosis in 11/19 (57.9%) patients in group 2. One female patient aged 37 years died due to a hepato-cellular carcinoma (HCC). Liver disease is present in the majority of older A-T patients. Structural changes, non-alcoholic fatty liver disease and fibrosis are frequent findings. Progress of liver disease is concomitant to neurological deterioration.
- Pre-emptive allogeneic hematopoietic stem cell transplantation in ataxia telangiectasia (2018)
- Ataxia telangiectasia (A-T) is a primary immunodeficiency with mutations in the gene encoding the A-T mutated (ATM) protein that interacts with immune, hematopoietic, and endocrine targets resulting in broad multi-systemic clinical manifestations with a devastating outcome. Apart from a progressive neurodegenerative disorder, A-T leads to significantly increased susceptibility to malignancies. It is a matter of discussion whether pre-emptive allogeneic hematopoietic stem cell transplantation (alloHSCT) using a reduced intensity conditioning regimen would be an option to restore immune-competence and prevent malignancy, as shown in animal models, because conventional treatment protocols of malignant diseases using radio- and/or chemotherapy have a high rate of therapy-related morbidity and mortality in these patients. We present the course of the disease, including immune reconstitution and neurological outcome following pre-emptive alloHSCT in a 4-year-old boy with A-T on a 6 year follow-up. Our manuscript provides a proof-of-concept of alloHSCT as an individual pre-emptive treatment strategy from which some A-T patients might benefit.
- The incidence and type of cancer in patients with ataxia-telangiectasia via a retrospective single-centre study (2021)
- Ataxia-telangiectasia (A-T) is a hereditary immune system disorder with neurodegeneration. Its first neurologic symptoms include ataxic gait in early childhood, with slowly progressive cerebellar ataxia, oculomotor apraxia, oculocutaneous telangiectasia, and progressive muscle weakness. Neonatal screening for severe T-cell deficiency was recently found to diagnose A-T patients with a significantly reduced naïve T-cell pool. Our study includes 69 A-T patients between 8 January 2002 and 1 December 2019. Nineteen cases of cancer were diagnosed in 17 patients (25%), with a median overall survival [OS; 95% cumulative indcidence (CI)] of 26·9 years for the entire cohort. The 15-year OS of 82·5% (72–95%) was significantly decreased among A-T patients with malignancies, who had a median OS of 2·11 years, with a two-year-estimated OS of 50·7% (31–82%). Haematological malignancies were the major causes of death within the initial years of life with a 15 times increased risk for death [HR (95% CI): 6·9 (3·1–15.2), P < 0·001] upon malignancy diagnosis. Male patients with A-T are at a higher cancer risk than their female counterparts. This manuscript highlights the need for cancer surveillance and prevention, as well as optimal treatment in this cohort.
