Clinical challenges following early detection of ataxia telangiectasia through SCID newborn screening

Ataxia telangiectasia (AT) is a rare autosomal recessive disease with progressive cerebellar neurodegeneration, variable degree of (combined) immunodeficiency, and increased risk of lymphoid malignancies. Especially patients with the hyper-IgM phenotype (HIGM-AT) are at risk for early-onset infections, cancer, and poor survival. AT can be a secondary finding in the T cell receptor excision circles (TRECs) based newborn screening for severe combined immunodeficiency, resulting in an early AT diagnosis, which poses challenges with respect to clinical management. It is yet unclear whether the positive TREC screening result is indicative for increased risk of the HIGM-AT phenotype. Here, we review the available literature on newborn screening outcomes and neonatal TREC levels in patients with AT. In addition, we discuss the available symptomatic treatment options for AT, including preemptive hematopoietic stem cell transplantation (HSCT), gene therapy, nicotinamide riboside (vitamin B3), and corticosteroids. Ultimately, we hope this article sparks international collaboration and prospective studies of newborn screening–identified patients with AT, focusing on outcomes and management.