Abnormal Newborn Screen in a WHIM Syndrome Infant

  • Martin O. EvansIIEmail author
  • David H. McDermott
  • Philip M. Murphy
  • Maureen M. Petersen
Letter to Editor

To the Editor,

T cell receptor excision circle (TREC) quantification was added to newborn screening in 2008 to identify newborns with severe combined immunodeficiency (SCID). However, the vast majority of infants identified by TREC screening do not have SCID on confirmatory testing [1]. Because of the novelty of the test, there is a paucity of information regarding long-term prognosis and differential diagnosis of non-SCID infants with low TREC levels. Here we present a case of warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome that presented on newborn screen with low TREC levels.

A full-term white male was born to a mother with WHIM syndrome, a rare autosomal dominant immunodeficiency disorder caused by gain-of-function CXCR4 mutations that are characterized by panleukopenia due to abnormal leukocyte distribution. The infant developed fever, tachypnea, and hypoxia 30 h after birth and was admitted to the neonatal intensive care unit for empiric intravenous...



Absolute lymphocyte count


Absolute neutrophil count


Cycle threshold number


C-X-C chemokine receptor type 4


C-X-C motif chemokine 12


Dried blood spots


Newborn screen


Ribonuclease P


Severe combined immunodeficiency


T cell receptor excision circles


White blood count


Whole-genome sequencing


Warts, hypogammaglobulinemia, infections, myelokathexis



I would like to acknowledge Adam Coleman, PhD at the Maryland Department of Health Laboratories Administration for his invaluable contribution to this work; his contribution included sample processing and data collection.

Author’s Contributions

ME, MP, and DM provided the medical care for the patient; DM and PM performed the gene sequencing, and ME, MP, PM, and DM wrote the manuscript. All authors read and approved the final manuscript.

Funding Information

This work was supported in part by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA.

National Institute of Allergy and Infectious Diseases, National Institutes of Health funded CXCR4 gene sequencing.

Compliance with Ethical Standards

Informed consent was obtained from the parents.

Conflict of Interest

The authors declare that they have no conflicts of interest.


The views expressed in this manuscript are those of the authors and do not reflect the official policy of the Department of Army/Navy/Air Force, Department of Defense, or U.S. Government.

Supplementary material

10875_2019_686_MOESM1_ESM.docx (14 kb)
ESM 1 (DOCX 13 kb)


  1. 1.
    Amatuni G, Currier R, Church J, Bishop T, Grimbacher E, Nguyen A, et al. Newborn screening for severe combined immunodeficiency and T-cell lymphopenia in California, 2010-2017. Pediatrics. 2019;143:2.CrossRefGoogle Scholar
  2. 2.
    Albin-Leeds S, Ochoa J, Mehta H, Vogel BH, Caggana M, Bonagura V, et al. Idiopathic T cell lymphopenia identified in New York state newborn screening. Clin Immunol. 2017;183:36–40.CrossRefGoogle Scholar
  3. 3.
    Gaballa A, Sundin M, Stikvoort A, Abumaree M, Uzunel M, Sairafi D, et al. T cell receptor excision circle (TREC) monitoring after allogeneic stem cell transplantation; a predictive marker for complications and clinical outcome. Int J Mol Sci. 2016;17:1705–22.CrossRefGoogle Scholar
  4. 4.
    Heusinkveld L, Majumdar S, Gao J, McDermott D, Murphy P. WHIM syndrome: from pathogenesis towards personalized medicine and cure. J Clin Immunol. 2019.Google Scholar
  5. 5.
    Dotta L, Notarangelo L, Moratto D, Kumar R, Porta F, Soresina A, et al. Long-term outcome of WHIM syndrome in 18 patients: high risk of lung disease and HPV-related malignancies. J Allergy Clin Immunol Pract. 2019;7(5):1568–77.CrossRefGoogle Scholar

Copyright information

© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2019

Authors and Affiliations

  1. 1.Walter Reed National Military Medical CenterBethesdaUSA
  2. 2.National Institute of Allergy and Infectious DiseasesNational Institutes of HealthBethesdaUSA

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