DiGeorge Syndrome (DGS)/Thymic Aplasia (N Engl J Med 2000;343:1313)
• Definition (J Pediatr 2001;139:715)
• Thymic and parathyroid aplasia/hypoplasia w/ ↓ T cells and frequent opportunistic infections as well as hypocalcemia, presents neonatally
• Divided into partial and complete types: 1% of pts have complete DGS (a form of SCID) w/ severe immunodeficiency; pts w/ partial DGS have milder immunodeficiency
• Pathophysiology: Embryologically 3rd and 4th pharyngeal pouches form incorrectly
• Microdeletion of 22q11.2 is the most common defect, generally de novo mutation
• Epidemiology: 1:4000 to 1:6000 prevalence
• Clinical manifestations: P/w tetany/szrs 2/2 hypocalcemia in 1st few days of life
• All T-cell def generally present within 1st 1–3 mo of age w/ opportunistic infections, viral infections, fungal infections (PCP), intracellular bacteria
• Can have similar facies to fetal alcohol syndrome: Short filtrum, low set ears
• Diagnostic studies: Absolute lymphocyte count ↓, B-cell count ↑, Ig nml
• ↓ mitogen stimulation response, can have delayed hypersensitivity skin testing
• Management: Bone marrow transplant w/ HLA match
• Thymic transplant in neonatal period (N Engl J Med 1999;341:1180)
• Complications: Can have other structural anomalies; conotruncal cardiac anomalies, right-sided aortic arch, esophageal atresia, bifid uvula, congenital heart disease, hypertelorism, mandibular hypoplasia, low set ears
• GVHD to nonirradiated blood products or to BMT with T cells