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

Christofer Äng; Rolf H Zetterström; Kim Ramme; Emma Axelsen; Per Marits; Mikael Sundin

doi:10.3389/fimmu.2023.1257581

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.

Authors

Christofer Äng^{1

2}, Rolf H Zetterström^{3

4}, Kim Ramme^{5

6}, Emma Axelsen⁷, Per Marits⁸, Mikael Sundin^{2

7}

Affiliations

¹ Sachs Children's Hospital, Södersjukhuset, Stockholm, Sweden.
² Division of Pediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
³ Center for Inherited Metabolic Diseases, Medical Diagnostics Center, Karolinska University Hospital, Stockholm, Sweden.
⁴ Division of Inborn Errors of Endocrinology and Metabolism, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
⁵ Department of Pediatric Hematology and Oncology, Children's Hospital, Uppsala University Hospital, Uppsala, Sweden.
⁶ Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
⁷ Section of Pediatric Hematology, Immunology and HCT, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
⁸ Department of Clinical Immunology, Medical Diagnostics Center, Karolinska University Hospital, Stockholm, Sweden.

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).