TREC Screening for WHIM Syndrome

Martin Oman Evans*, Maureen M. Petersen, Amer Khojah, Soma C. Jyonouchi, George S. Edwardson, Yasmin West Khan, James Albert Connelly, David Morris, Shamik Majumdar, David H. McDermott, Jolan E. Walter, Philip M. Murphy

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Purpose: T cell receptor excision circle (TREC) quantification is a recent addition to newborn screening (NBS) programs and is intended to identify infants with severe combined immunodeficiencies (SCID). However, other primary immunodeficiency diseases (PID) have also been identified as the result of TREC screening. We recently reported a newborn with a low TREC level on day 1 of life who was diagnosed with WHIM (warts, hypogammaglobulinemia, infections, myelokathexis) syndrome, a non-SCID primary immunodeficiency caused by mutations in the chemokine receptor CXCR4. Methods: We have now retrospectively reviewed the birth and clinical histories of all known WHIM infants born after the implementation of NBS for SCID. Results: We identified six infants with confirmed WHIM syndrome who also had TREC quantification on NBS. Three of the six WHIM infants had low TREC levels on NBS. All six patients were lymphopenic but only one infant had a T cell count below 1,500 cells/μL. The most common clinical manifestation was viral bronchiolitis requiring hospitalization. One infant died of complications related to Tetralogy of Fallot, a known WHIM phenotype. Conclusion: The results suggest that WHIM syndrome should be considered in the differential diagnosis of newborns with low NBS TREC levels. Trial Registration: Not applicable.

Original languageEnglish
Pages (from-to)621-628
Number of pages8
JournalJournal of Clinical Immunology
Issue number3
StatePublished - Apr 2021
Externally publishedYes


  • CXCR4
  • Tetralogy of Fallot
  • neutropenia
  • newborn screen


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