Artemis Deficiency (SCID with Leukopenia): Genetics, Immunology, and Treatment

Artemis deficiency is a rare autosomal recessive form of severe combined immunodeficiency (SCID) caused by mutations in the DCLRE1C gene (chromosome 10p). The Artemis protein is essential for V(D)J recombination—the process that generates diverse T-cell and B-cell receptors—and for DNA double-strand break repair via non-homologous end joining (NHEJ).

Clinical Features

• Profound T-cell and B-cell lymphopenia (low or absent)
• Recurrent, severe infections (bacterial, viral, fungal) starting in infancy
• Failure to thrive, chronic diarrhea, skin rashes
• Increased sensitivity to ionizing radiation and chemotherapeutic agents

Diagnosis

Newborn screening (TREC assay) detects low T-cells. Confirmation: flow cytometry (CD3+, CD19+ counts), genetic testing for DCLRE1C mutations.

Treatment

Hematopoietic stem cell transplantation (HSCT) from a matched donor is curative. Best outcomes with early transplant (<3.5 months) and reduced-intensity conditioning. Gene therapy (lentiviral vector) is in clinical trials. Supportive care: immunoglobulin replacement, antimicrobial prophylaxis, avoidance of live vaccines.

Early diagnosis via newborn screening dramatically improves survival.