neonatal screening of severe combined immunodeficiencies

Conditions: Severe Combined Immunodeficiency; Neonatal Screening

Summary: the goal of the proposed research is to observe the prevalence and establish the validity of a newborn screening method for severe combined immunodeficiency (scid). the assay to be used is developed on the basis of pcr quantification of t-cell receptor excision circles (trecs) that is absent in scid patients, thus correlating with the disease.

severe combined immunodeficiencies (scid) are a group of inherited diseases of the immune system by characterized profound abnormalities of b and t cell development. infants with scid require prompt clinical response to prevent life threatening infection and studies show significantly improved survival in babies diagnosed at birth as a result of previous family history. scid follows criteria for population based newborn screening since it is asymptomatic at birth and fatal within the first year of life, the confirmation of the disease is easy, there is a curative treatment, and it is known that early stem cell transplantation improves survival.to show that early diagnosis of scid with a trec screening assay can warrant timely treatment of the disease and avoid life-threatening infections on patients. babies with scid are unable to fight infections. they become severely ill in their first months of life and do not survive unless their immune systems can be restored. scid can be treated by bone marrow transplant if recognized early. we undertake the task of newborn screening in the whole region of shanghai, so the newborn screening test to be employed in this study is designed to diagnose scid before infections occur. through this study, we hope to confirm the prevalence of scid in china and the benefits of newborn screening for early diagnosis of scid. quantification of trecs (t-cell receptor excision circles) in dna extracted from guthrie samples is a sensitive screening test for specific and scid. trecs are small-circle dna molecules which are by-products of t cell maturation in the thymus, and their numbers reflect the number of recently emigrated t-cells from the thymus. since all infants with scid have a profound decrease in t-lymphocytes no matter what gene mutations are involved, logically the number of trecs present in blood collected via dried blood spots 1-2 days post delivery on scid babies should be very low when compared with healthy newborns. the trec assay includes dna extraction from a 3 mm punch of dried blood specimen in a 96-well plate format. the extracted dna undergoes real-time qpcr procedure on 7900 ht fast real-time pcr system (abi). the trec copy number is calculated relative to a standard curve generated from serially diluted plasmids which contain a known number of trec. the investigators propose in this study to perform a neonatal screening of scid, in a population of 200,000 babies over a period of three years. the investigators propose to study the incidence of scid, mortality \& rate of disability, clinical utility and scid screening to demonstrate that could result in a broad benefit to individuals detected, making screening relatively efforts in spite of the low incidence of the disease.

Eligibility criteria:
inclusion criteria: 1. no more than 28 days old 2. newborns who was born in shanghai and in 2016 to 2020 3. blood sample card was collected in 72 hours after birth exclusion criteria: 1. lack of parental consent 2. sample card was damaged

Keywords: neonatal screening severe combined immunodeficiency immunologic deficiency syndromes dna repair-deficiency disorders t-cell receptor excision circle