Chapter 15 - Early Diagnosis of Severe Combined Immunodeficiency

Abstract

Severe combined immunodeficiency (SCID) is fatal unless corrected early with hematopoietic stem cell transplantation (HSCT) or gene therapy (GT) early in life. SCID patients are asymptomatic 4 to 6 months after birth secondary to protective maternal antibodies. If undiagnosed in the asymptomatic period, patients will develop severe, often fatal infections. Early diagnosis of SCID with newborn screening (NBS) in the asymptomatic period is key to the prevention of fatal infections and improved transplant outcomes. NBS for SCID that uses measurement of T-cell receptor excision circles (TRECs) is feasible. Immunologic testing is required to confirm the SCID diagnosis after a positive NBS result. Genetic screening is essential to determine the best treatment strategy and help with family planning. Interim treatment regimens with antibacterial, viral, and fungal prophylaxis and immunoglobulin and/or enzyme replacement therapy (ERT) are essential for patients diagnosed with SCID in the asymptomatic stage. Definitive treatment strategies include HSCT, GT, and ERT in select cases (e.g., adenosine deaminase deficiency). NBS using TREC measurement can identify patients with T-cell lymphopenias other than SCID. Patients with non-SCID T-cell lymphopenia who are diagnosed with SCID by NBS require further workup for primary and secondary causes. Early diagnosis of ataxia-telangiectasia using NBS for SCID is an ethical dilemma. It is unclear if NBS for SCID is economically feasible in developing countries.