Severe Combined Immunodeficiencies (SCID) are disorders with defective cellular and humoral immunity. In typical SCID, T Cell Receptor Excision Circles (TRECs) are absent; thus, TREC analysis has become part of the newborn screening panel of several states. Whether TREC screening can detect leaky SCID and improve outcome is less clear. We retrospectively analyzed two patients with leaky SCID.
SCID genes were sequenced. DNA from archived neonatal dried blood spots (DBS) was used for quantitative PCR for TRECs and genomic B-actin.
Patient 1, diagnosed in infancy with agammaglobulinemia requiring IVIG, had low CD4 cells, recurrent infections, alopecia, eczema, gastrointestinal inflammation and pulmonary disease. At age 17, a novel homozygous RAG2 gene truncation mutation (E407X) was found. Patient 2, diagnosed in childhood with common variable immunodeficiency, had warts, recurrent fungal skin infections and bronchiectasis, despite IVIG. At age 8, T lymphopenia and diminished proliferation were documented, as was a known leaky SCID missense mutation IL2RG(R222C). Patient 1 had 15 TREC/uL (low) and patient 2 had undetectable TRECs. Both patients had normal B-actin controls. Patient 1 was cured with a matched sibling Hematopoietic Cell Transplant (HCT). Patient 2 received two HCTs but failed to engraft and succumbed to infection.
Delayed recognition of leaky SCID caused significant childhood morbidity in both patients, one of whom did not survive HCT. Retrospective testing showed that both could have been diagnosed early in life before infectious or autoimmune complications if TREC newborn screening had been available. Thus, TREC newborn screening is potentially beneficial for leaky SCID.
- AAAAI 2013 (69th)