Abstract
Simple SummaryAtaxia-Telangiectasia is a rare neurodegenerative disease and patients die in their early forties mainly because of immunodeficiency, leukemia and lymphoma. In this work we describe the different routes of diagnosis, the recent treatments, and the emerging therapies for the disease. Bone marrow transplantation from siblings or an unrelated donor is becoming an option of therapy for selected Ataxia-Telangiectasia patients to deal with the immunodeficiency and to prevent leukemia and lymphoma. The patients require a non-myeloablative conditioning before bone marrow transplantation because they are radiosensitive to ionizing radiations and radiomimetics. The eligibility of patients for transplantation such as the range of age, spectrum of clinical features, and conditioning are still to be determined, transplant protocol guidelines must be defined and longer follow-ups are necessary to evaluate the risks and side effects associated with transplantation.Ataxia-Telangiectasia (A-T) is a rare autosomal recessive disorder, first reported in 1926, caused by a deficiency of ATM (Ataxia-Telangiectasia Mutated) protein. The disease is characterized by progressive cerebellar neurodegeneration, immunodeficiency, leukemia, and lymphoma cancer predisposition. Immunoglobulin replacement, antioxidants, neuroprotective factors, growth, and anti-inflammatory hormones are commonly used for A-T treatment, but, to date, there is no known cure. Bone marrow transplantation (BMT) is a successful therapy for several forms of diseases and it is a valid approach for tumors, hemoglobinopathies, autoimmune diseases, inherited disorders of metabolism, and other pathologies. Some case reports of A-T patients have shown that BMT is becoming a good option, as a correct engraftment of healthy cells can restore some aspects of immunologic capacity. However, due to a high risk of mortality as a result of a clinical and cellular hypersensitivity to ionizing radiation and radiomimetic drugs, a specific non-myeloablative conditioning is required before BMT. Although BMT might be considered as one promising therapy for the treatment of immunological defects and cancer prevention in selected A-T patients, the therapy is currently not recommended or recognized and the eligibility of A-T patients for BMT is a point to deepen and deliberate.
Highlights
Ataxia-Telangiectasia (A-T) is a rare autosomal recessive disorder, characterized by a progressive cerebellar neurodegeneration, immunodeficiency, infertility, and cancer predisposition, with high incidence of leukemia and lymphoma [1,2]
Allo-hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for several hematologic and immunological diseases, it is known that side effects including chronic GVHD, infectious and secondary malignancies occur in the long-term period post-transplantation [56]
Primary immunodeficiency of Ataxia-Telangiectasia might ameliorate after bone marrow transplantation and cancer prevention can be observed
Summary
Ataxia-Telangiectasia (A-T) is a rare autosomal recessive disorder, characterized by a progressive cerebellar neurodegeneration, immunodeficiency, infertility, and cancer predisposition, with high incidence of leukemia and lymphoma [1,2]. The kinase functions as a guardian of genome integrity acting on cell-cycle checkpoints, apoptosis, gene expression, and DNA repair after DNA double-strand breaks (DSBs) [4]. ATM acts as a DSB transducer activating a plethora of downstream effectors and orchestrating the DNA damage response [4]. Due to their critical role in genome stability, ATM mutations cause several body system malfunctions [6]. Bone marrow transplantation (BMT) is a potential therapeutic approach for A-T patients, as reconstitution of cells with functional ATM can rescue some aspects of immunodeficiency [1,7,10]. A-T children recently subjected to BMT from siblings or matched unrelated donors
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