Prospective Newborn Screening for SCID in Germany: A First Analysis by the Pediatric Immunology Working Group (API)

J Clin Immunol. 2023 Jul;43(5):965-978. doi: 10.1007/s10875-023-01450-6. Epub 2023 Feb 27.

Abstract

Backgr ound: T-cell receptor excision circle (TREC)-based newborn screening (NBS) for severe combined immunodeficiencies (SCID) was introduced in Germany in August 2019.

Methods: Children with abnormal TREC-NBS were referred to a newly established network of Combined Immunodeficiency (CID) Clinics and Centers. The Working Group for Pediatric Immunology (API) and German Society for Newborn Screening (DGNS) performed 6-monthly surveys to assess the TREC-NBS process after 2.5 years.

Results: Among 1.9 million screened newborns, 88 patients with congenital T-cell lymphocytopenia were identified (25 SCID, 17 leaky SCID/Omenn syndrome (OS)/idiopathic T-cell lymphocytopenia, and 46 syndromic disorders). A genetic diagnosis was established in 88%. Twenty-six patients underwent hematopoietic stem cell transplantation (HSCT), 23/26 within 4 months of life. Of these, 25/26 (96%) were alive at last follow-up. Two patients presented with in utero onset OS and died after birth. Five patients with syndromic disorders underwent thymus transplantation. Eight syndromic patients deceased, all from non-immunological complications. TREC-NBS missed one patient, who later presented clinically, and one tracking failure occurred after an inconclusive screening result.

Conclusion: The German TREC-NBS represents the largest European SCID screening at this point. The incidence of SCID/leaky SCID/OS in Germany is approximately 1:54,000, very similar to previous observations from North American and European regions and countries where TREC-NBS was implemented. The newly founded API-CID network facilitates tracking and treatment of identified patients. Short-term HSCT outcome was excellent, but NBS and transplant registries will remain essential to evaluate the long-term outcome and to compare results across the rising numbers of TREC-NBS programs across Europe.

Keywords: HSCT; Hematopoietic stem cell transplantation; NBS; Newborn screening; SCID; Severe combined immunodeficiency; T cell receptor excision circles; TREC; Thymus transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • DNA
  • Germany / epidemiology
  • Humans
  • Infant, Newborn
  • Lymphopenia* / diagnosis
  • Neonatal Screening / methods
  • Prospective Studies
  • Receptors, Antigen, T-Cell / genetics
  • Severe Combined Immunodeficiency* / diagnosis
  • Severe Combined Immunodeficiency* / epidemiology
  • Severe Combined Immunodeficiency* / therapy

Substances

  • DNA
  • Receptors, Antigen, T-Cell