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. 2021 Apr;41(3):621-628.
doi: 10.1007/s10875-020-00921-4. Epub 2021 Jan 7.

TREC Screening for WHIM Syndrome

Martin Oman Evans 2nd  1 , Maureen M Petersen  2 , Amer Khojah  3 , Soma C Jyonouchi  4 , George S Edwardson  5 , Yasmin West Khan  6 , James Albert Connelly  6 , David Morris  7 , Shamik Majumdar  8 , David H McDermott  8 , Jolan E Walter  9   10 , Philip M Murphy  8
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TREC Screening for WHIM Syndrome

Martin Oman Evans 2nd et al. J Clin Immunol. 2021 Apr.

Erratum in

  • Correction to: TREC Screening for WHIM Syndrome.
    Oman Evans M 2nd, Petersen MM, Khojah A, Jyonouchi SC, Edwardson GS, Khan YW, Connelly JA, Morris D, Majumdar S, McDermott DH, Walter JE, Murphy PM. Oman Evans M 2nd, et al. J Clin Immunol. 2021 Apr;41(3):629-630. doi: 10.1007/s10875-021-00976-x. J Clin Immunol. 2021. PMID: 33506316 Free PMC article. No abstract available.

Abstract

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.

Keywords: CXCR4; Tetralogy of Fallot; neutropenia; newborn screen.

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Conflict of interest statement

Disclosure of Conflicts of Interest:

Related:

J.E.W. has received grants as principal investigator on investigator-initiated translational studies and sponsored clinical trials of patients with WHIM syndrome funded by X4 Pharmaceuticals.

Unrelated:

J.E.W. has been an advisory board member, speaker bureau participant and site-principal investigator for a trial funded by Takeda (former Shire) outside of the submitted work.

J.E.W. has also run sponsored studies for Lediant, Octapharma and Momenta as site principal investigator outside of the submitted work.

References

    1. Beaussant Cohen S, Fenneteau O, Plouvier E, et al. Description and outcome of a cohort of 8 patients with WHIM syndrome from the French Severe Chronic Neutropenia Registry. Orphanet J Rare Dis. 2012;7:71. Published 2012 Sep 25. - PMC - PubMed
    1. Aghamohammadi A, Abolhassani H, Puchalka J, et al. Preference of Genetic Diagnosis of CXCR4 Mutation Compared with Clinical Diagnosis of WHIM Syndrome. J Clin Immunol. 2017;37(3):282–286. - PubMed
    1. Heusinkveld LE, Majumdar S, Gao JL, McDermott DH, Murphy PM. WHIM Syndrome: from Pathogenesis Towards Personalized Medicine and Cure. J Clin Immunol. 2019;39(6):532–556. doi:10.1007/s10875-019-00665-w - DOI - PMC - PubMed
    1. Evans MO 2nd, McDermott DH, Murphy PM, Petersen MM. Abnormal Newborn Screen in a WHIM Syndrome Infant. J Clin Immunol. 2019;39(8):839–841. doi:10.1007/s10875-019-00686-5 - DOI - PMC - PubMed
    1. Mentzer WC, Johnston RB, Baehner RL, Nathan DG. An unusual form of chronic neutropenia in a father and daughter with hypogammaglobulinaemia. Br J Haematol 1977;36:313–22. - PubMed

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