Case report: IKZF1-related early-onset CID is expected to be missed in TREC-based SCID screening but can be identified by determination of KREC levels

Front Immunol. 2023 Sep 12:14:1257581. doi: 10.3389/fimmu.2023.1257581. eCollection 2023.

Abstract

This report illustrates a case that would have been missed in the most common screening algorithms used worldwide in newborn screening (NBS) for severe combined immunodeficiency (SCID). Our patient presented with a clinical picture that suggested a severe inborn error of immunity (IEI). The 6-month-old baby had normal T-cell receptor excision circle (TREC) levels but no measurable level of kappa-deleting recombination excision circles (KRECs) in the NBS sample. A de novo IKZF1-mutation (c.476A>G, p.Asn159Ser) was found. The clinical picture, immunologic workup, and genetic result were consistent with IKZF1-related combined immunodeficiency (CID). Our patient had symptomatic treatment and underwent allogeneic hematopoietic cell transplantation (HCT). IKZF1-related CID is a rare, serious, and early-onset disease; this case provides further insights into the phenotype, including KREC status.

Keywords: CID; HCT (hematopoietic cell transplant); IKZF1; Ikaros; SCID; newborn screening.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Ikaros Transcription Factor / genetics
  • Infant
  • Infant, Newborn
  • Neonatal Screening
  • Phenotype
  • Severe Combined Immunodeficiency* / diagnosis
  • Severe Combined Immunodeficiency* / genetics
  • Severe Combined Immunodeficiency* / therapy

Substances

  • IKZF1 protein, human
  • Ikaros Transcription Factor

Grants and funding

The authors declare that financial support was received for the research of this article from the Samariten Foundation for Pediatric Research (Grant# 2022-21197).