![]() ![]() ( 5– 7)īecause SCID is rare and affected infants appear healthy at birth, and the majority of cases have no recognized positive family history, population-based newborn screening was turned to as a strategy to identify infants with SCID sufficiently early in life to provide treatment before the onset of infectious complications. ( 1, 2, 4– 7) Best outcomes are achieved if infants are treated early to avoid infectious complications, as documented by single center reports ( 8) and by retrospective and prospective multicenter studies from the Immune Deficiency Foundation ( 9) and Primary Immune Deficiency Treatment Consortium (PIDTC). In addition, enzyme replacement therapy (ERT) is available for adenosine deaminase (ADA) deficient SCID, and autologous hematopoietic cell correction by gene therapy (GT) has been successful for ADA deficient and X-linked SCID, with Artemis-deficient SCID also being tested in a clinical trial. Haplo-identical parental bone marrow or mobilized peripheral blood hematopoietic stem cells (PBSC) depleted of T cells have been used, ( 4) as well as closely matched bone marrow, PBSCs or cord blood from unrelated donors. ( 3) Advances in allogeneic hematopoietic cell transplantation (HCT) have been pioneered in SCID since that time, with effective treatment, at least with restoration of T cell numbers and function, accomplished by HCT from not only matched siblings, but also from alternative donors. ( 1, 2) SCID was uniformly fatal in the first year of life prior to 1968, when the first successful treatment was reported in a male infant who received a transplant of bone marrow from his healthy, HLA-matched sibling. Individuals affected with SCID have absent or very low numbers of T cells and absent or nonfunctional B cells, rendering them susceptible to life-threatening bacterial, fungal and viral infections with both ordinary and opportunistic pathogens. Severe combined immunodeficiency (SCID) is the term used to describe at least 20 known, and additional unknown, rare genetic disorders in which both T and B cell immunity, the components of the adaptive immune system, are lacking. Previously unknown immune defects have been discovered, as well as conditions not formerly recognized to have low T cells in the neonatal period. Experience has accumulated regarding the range and limitations of diagnoses of newborns with low TRECs and low T cells. ![]() In addition to bringing to attention infants with the primary screening target diseases, typical SCID and leaky SCID (due to hypomorphic mutations in known SCID genes), the newborn screening assay for insufficient TRECs in dried blood spots also reveals infants with non-SCID T lymphopenic conditions. It has proven effective, with infants having this otherwise inapparent but serious, rare disorder achieving survival and immune reconstitution. SCID screening is now the accepted standard of care in state public health departments across the USA, and it is being adopted in many countries. Upon being flagged by an abnormal screening test in a SCID screening program, an infant can receive further diagnostic testing for SCID in the neonatal period, prior to onset of infectious complications, to pemit immediate institution of protective measures and definitive, life-saving treatment to establish a functional immune system. The development of a T cell receptor excision circle (TREC) assay utilizing dried blood spots made possible universal newborn screening (NBS) for severe combined immunodeficiency (SCID) as a public health measure. ![]()
0 Comments
Leave a Reply. |