The document outlines various immunodeficiencies, including 'pure' T and B cell disorders, severe combined immunodeficiencies (SCID), and related genetic conditions. It describes the clinical manifestations, genetic factors, and potential treatments such as bone marrow transplantation and gene therapy. Specific syndromes like DiGeorge syndrome, X-linked SCID, and others are mentioned along with their respective symptoms and associated genetic anomalies.

2. ZAP 70 ADA ADA PNP PNP

3. “ Pure” T Cell Disorders “ Pure” B Cell Disorders Severe Combined Immunodeficiency (SCID) Combined Immunodeficiencies Phagocyte Deficiencies Complement Deficiencies

4. B Cell: recurrent sinopulmonary and GI infections beginning after 3-4 mo. T Cell and Severe Combined Immunodeficiency (SCID): opportunistic infections beginning early in infancy (thrush, diarrhea, failure to thrive); Milder forms termed Combined Immunodeficiency (CID) Phagocyte deficiencies: deep tissue infections with high-grade bacterial pathogens Complement: some infections, primarily with encapsulated organisms and Neisseriae

5. “ Pure” T Cell Deficiencies: DiGeorge syndrome T cell receptor deficiencies Zap 70 deficiency

6. Conotruncal cardiac malformation Hypoparathyroidism Thymic hypoplasia leading to variable immunodeficiency Other features: Characteristic facies Deletion in 22q11 in > 80% Affected gene(s) is a transcription factor in the T-box family called Tbx1

8. Interrupted aortic arch 27% Truncus arteriosus 25% Tetrology of Fallot 22%

11. X-linked SCID (  c deficiency) Jak3 kinase deficiency Adenosine deaminase deficiency Purine nucleoside phosphorylase deficiency Bare lymphocyte syndrome RAG1 and RAG2 deficiency

12. Failure to thrive Onset of infections in the neonatal period Opportunistic infections Chronic or recurrent thrush Chronic rashes Chronic or recurrent diarrhea Paucity of lymphoid tissue

13. Hypogammaglobulinemia Absence of antibody responses to immunizations Absent mitogen responses Low or absent T cells Often low or absent B cells

14. Bone marrow transplantation, preferably from a histocompatible sibling Gene therapy

15. Most common form of SCID (40%) Very low T cells and NK cells with low to normal numbers of B cells Responsible gene:  c – the common subunit of receptors for IL-2, IL-4, IL-7, IL-9, and IL-15

17. Bruton’s (X-linked) Agammaglobulinemia Autosomal Recessive Hyper-IgM Syndrome B Cell Receptor Deficiencies Common Variable Immunodeficiency (CVID) Selective IgA Deficiency IgG Subclass Deficiency

18. IgA deficiency frequently coexists with IgG subclass deficiency, especially IgG2 and IgG4 Linkage to Class III region of HLA 50% incidence of IgA-D in children of patients with CVID Occasionally IgA deficient patients have been noted to progress to CVID

19. Panhypogammaglobulinemia, usually with lymphadenopathy and splenomegaly Absence of clear abnormalities in T and B cell subsets Chronic/recurrent respiratory infections, & diarrhea, especially due to Giardia Tendency to develop autoimmunity and lymphoid malignancies Linkage to HLA Class III Region in 2/3 of patients One gene identified: ICOS (B7h) (activation antigen on T cells)

20. Chronic/recurrent upper respiratory infections, especially sinusitis Tendency to develop respiratory and gastrointestinal allergies and autoimmunity

21. Wiskott-Aldrich Syndrome: thrombocytopenia, eczema, immunodeficiency Ataxia-Telangiectasia: DNA repair disorder X-linked Hyper-IgM Syndrome: inability to make other Ig isotypes X-linked Lymphoproliferative Disorder: immunodeficiency following EBV infection Hyper-IgE with Infections: markedly elevated IgE with deep-seated bacterial infections Chronic Mucocutaneous Candidiasis: chronic superficial fungal infections Genes identified

22. Chronic granulomatous disease (CGD) Leukocyte adhesion deficiency (LAD I) Chediak-Higashi syndrome IL-12/IFN  pathway deficiencies Chronic or cyclic neutropenia

23. Inability of phagocytes to generate hydrogen peroxide due to mutations in one of four proteins comprising the NADPH oxidase Severe tissue infections with catalase positive organisms, esp. Staph aureus, Serratia marcescens, mycobacteria, and fungi such as Aspergillus

24. Nitroblue tetrazolium (NBT) test or, more recently, flow cytometric tests using fluorescent dyes such as dihydrorhodamine (DHR)

25. Prophylaxis with antibiotics (bactrim and itraconazole) and gamma interferon Bone marrow transplant with HLA identical sibling Gene therapy (?)

27. Patient Mother Father DHR Flow Cytometric Assay

28. CGD patient with skin infections due to Serratia marcescens

29. Severe tissue infections due to absence of adhesion molecules (  -integrins CD11/CD18) on leukocytes Inability to make pus due to entrapment of phagocytes within the vasculature Lethal within the first decade of life without bone marrow transplant

30. Omphalitis in LAD I patient

31. Abnormal large granules in a variety of cells leading to: hypopigmentation/partial albinism severe immunodeficiency neurologic abnormalities mild bleeding tendencies Defective gene: CHS1 located on 1q42-43, protein product involved in granule trafficking

33. IL-12 receptor IL-12 IFN  R1 and IFN  R2 STAT-1 Pattern of infections: overwhelming infection with intracellular pathogens, esp. atypical mycobacteria

36. Rule I: In any inherited deficiency of a component of the classical pathway, total hemolytic activity (CH50) will be close to zero Rule II: In any inherited deficiency of a component of the alternate pathway, total hemolytic activity (AH50) will be close to zero