Snapshot A 2-month-old baby boy is brought in for an urgent visit to the pediatrician. He has had several ear infections in his short lifetime and now seems to be struggling with a cold. On physical exam, his tongue is noted to be coated with white film. His scalp and face are covered with a flaky dandruff-like substance. Immediately concerned, his pediatrician orders a chest radiograph, which shows absence of thymic shadow. Flow cytometry is ordered. Introduction Combined B- and T-cell disorder causing immunodeficiency Life-threatening disease of recurrent infections Pathogenesis multiple variants found most common is X-linked defective common gamma chain found in IL-2R, IL-4R, and IL-7R defective T-cell activation autosomal recessive adenosine deaminase deficiency 2nd most common ↑ deoxyadenosine, which is toxic to lymphocytes ↓ DNA synthesis autosomal recessive JAK3 deficiency B-cells decreased immunoglobulin production T-cells markedly decreased T-cells Presentation Symptoms symptoms present < 3 months of age failure to thrive recurrent bacterial, viral, fungal, and protozoal infections chronic diarrhea Physical exam may see thrush in mouth and diaper area eczematous dermatitis erythroderma (> 90% body surface area involvement) severe seborrheic dermatitis diffuse alopecia absent lymphatic tissue, including tonsils and thymus Evaluation Diagnosis often delayed due to maternal IgG protecting baby in first few months of life ↓ Lymphocyte count (< 3000/μL) Chest radiography with no thymic shadow Flow cytometry absent T-cells abnormal function of B-cells Differential Diagnosis Hypogammaglobulinemia DiGeorge syndrome Hyper-IgM syndrome Ataxia-telangiectasia Treatment Bone marrow transplant life-saving treatment no concerns for allograft rejection Gene therapy Prognosis, Prevention, and Complications Prognosis without intervention, death by 2 years patients < 6 months of age who receive transplant have the best outcomes Complications severe infection death