Neonatal Screening of Severe Combined Immunodeficiencies

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Brief Title

Neonatal Screening of Severe Combined Immunodeficiencies

Official Title

Generalized Neonatal Screening for Severe Combined Immunodeficiencies (SCID) by Quantification of TRECs

Brief 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.
    

Detailed Description

      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.
    


Study Type

Observational


Primary Outcome

prevalence of SCID

Secondary Outcome

 Number of detected SCID patients

Condition

Severe Combined Immunodeficiency


Study Arms / Comparison Groups

 Screened patients
Description:  SCID screening: some drops of blood are placed on a second Guthrie card when current screening is performed after parents' information and consent. The card drawn for the protocol will follow the usual network except that the test for quantifying TRECs will be realized to determine the presence of SCID.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information



Estimated Enrollment

200000

Start Date

December 2015

Completion Date

December 2020

Primary Completion Date

December 2020

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
      

Gender

All

Ages

N/A - 28 Days

Accepts Healthy Volunteers

No

Contacts

, , [email protected]

Location Countries

China

Location Countries

China

Administrative Informations


NCT ID

NCT02590328

Organization ID

NSSCID


Responsible Party

Principal Investigator

Study Sponsor

Children's Hospital of Fudan University


Study Sponsor

, , 


Verification Date

June 2019