Martin Oman Evans1, Maureen M Petersen2, Amer Khojah3, Soma C Jyonouchi4, George S Edwardson5, Yasmin West Khan6, James Albert Connelly6, David Morris7, Shamik Majumdar8, David H McDermott8, Jolan E Walter9,10, Philip M Murphy8. 1. Blanchfield Army Community Hospital, Fort Campbell, KY, USA. martin.o.evans.mil@mail.mil. 2. Walter Reed National Military Medical Center, Bethesda, MD, USA. 3. Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA. 4. Children's Hospital of Philadelphia, Philadelphia, PA, USA. 5. Wright-Patterson Medical Center, Wright-Patterson Air Force Base, Wright-Patterson AFB, OH, USA. 6. Vanderbilt University Medical Center, Nashville, TN, USA. 7. Dayton Children's Hospital, Dayton, OH, USA. 8. National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 9. University of South Florida and Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA. 10. Massachusetts General Hospital for Children, Boston, MA, USA.
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.
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.
Entities:
Keywords:
CXCR4; Tetralogy of Fallot; neutropenia; newborn screen
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