Delayed-Onset ADA1 (ADA) Deficiency Not Detected by TREC Screen
Basil M Kahwash1,2, Jennifer R Yonkof3,2, Roshini S Abraham2
1Division of Allergy and Immunology, Department of Otolaryngology, College of Medicine, The Ohio State University, Columbus, Ohio; and basil.kahwash@vumc.org.
Pediatrics
|May 12, 2021
Summary
Severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency can present later in infancy. Early recognition through complete blood counts is crucial for timely diagnosis and treatment of this rare genetic disorder.
Area of Science:
- Immunology
- Genetics
- Pediatrics
Background:
- Severe combined immunodeficiency (SCID) is a group of rare genetic disorders characterized by profound defects in the immune system.
- Newborn screening for SCID typically relies on T-cell receptor excision circle (TREC) analysis, which may not detect all forms of the disease.
Observation:
- A 9-month-old boy presented with failure to thrive, neutropenia, and profound lymphopenia, despite normal newborn screening.
- The patient experienced opportunistic infections including Pneumocystis jirovecii pneumonia, adenovirus, and rotavirus.
- Enzyme assays revealed absent adenosine deaminase (ADA) activity, and genetic sequencing identified pathogenic variants in the ADA gene.
Findings:
- The patient was diagnosed with adenosine deaminase deficiency-severe combined immunodeficiency (ADA-SCID), a genetic disorder caused by mutations in the ADA gene.
- Hypomorphic ADA variants can lead to delayed-onset SCID, potentially being missed by standard newborn screening methods.
- Complete blood cell count abnormalities, specifically lymphopenia, can serve as an important diagnostic clue.
Implications:
- Prompt diagnosis and management, including enzyme replacement therapy (Revcovi) and hematopoietic cell transplantation, are critical for improving outcomes in ADA-SCID.
- Increased awareness and careful review of complete blood counts may aid in identifying infants with SCID who were missed by newborn screening.
- Understanding the genetic basis of ADA-SCID informs genetic counseling and long-term management strategies.
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