Immune Deficiencies

Question 1

X-linked Agammaglobulinemia (Bruton)

Answer 1

B-cell disorder
Defect: BTK gene, no B cell maturation, X-linked Recessive
Presentation: Recurrent bacterial infections after 6 months of age, absent/scanty lymph nodes/tonsils, low Ig of all classes but normal CD19+ B cell count

Question 2

Selective IgA deficiency

Answer 2

B cell disorder
Defect: unknown
Presentation: Asymptomatic, but can see airway/GI infections, autoimmune associations, atopy, anaphylaxis to IgA-containing products

Question 3

Common variable immunodeficiency

Answer 3

B cell disorder
Defect: B cell differentiation
Presentation: 20-30yo with decreased plasma cells and Ig, risk of autoimmune, bronchiectatis, lymphoma, sinopulm infections

Question 4

Digeorge Syndrome

Answer 4

T cell disorder
Defect: 22q11 deletion, failed devt of 3rd-4th pharyngeal pouches > absent thymus and parathyroids
Presentation: Absent thymic shadow, recurrent viral/fungal infxns, tetany (hypocalcemia), conotruncal abnormalities (TOF, truncus arteriosus)

Question 5

IL-12 Receptor Deficiency

Answer 5

T cell disorder
Defect: Decreased Th1 response (less cell-mediated immunity)
Presentation: Disseminated mycobacterial and fungal infxn, decreased IFN-gamma

Question 6

Hyper IgE Syndrome (Job)

Answer 6

T cell disorder
Defect: Autosomal dom mutation in STAT3 gene, Th17 deficiency > impaired PMN recruitment
Presentation: FATED = coarse Facies, cold staph Abscesses, primary Teeth, high IgE, Derm issues (eczema) + decreased IFN-gamma

Question 7

SCID

Answer 7

B and T cell disorder
Defect: defective IL2-receptor gamma chain (x-linked) or defective adenosine deaminase (autosomal recessive)
Presentation: Failure to thrive, chronic diarrhea, thrush, recurrent bacterial/viral/fungal/protozoal infxns, decreased T-cell receptor excision circles, no thymic shadow, germinal centers on node biopsy

Question 8

Ataxia-Telangiectasia

Answer 8

B and T cell disorder
Defect: ATM gene > DNA ds breaks > cell cycle arrest
Presentation: Triad = spider angioma (telangiectasia), IgA deficiency, ataxia; Increased AFP, decreased Ig, cerebellar atrophy

Question 9

Hyper IgM Syndrome

Answer 9

B and T cell disorder
Defect: X-linked recessive defect of CD40L on Th cells, no class switching
Presentation: severe pyogenic infxn, Pneumocystis, Cryptosporidium, CMV; High IgM, Low IgG, IgA, IgE

Question 10

Wiskott-Aldrich Syndrome

Answer 10

B and T cell Disorder
Defect: X-linked recessive WAS gene mutation, T cells cannot reorganize actin skeleton
Presentation: WATER = Wiskott Aldrich Thrombocytopenia, Eczema, Recurrent infxns. High IgE and IgA, low IgG and IgM. Small platelets. Increased risk of autoimmune and malignancy

Question 11

Leukocyte Adhesion Deficiency 1

Answer 11

Phagocyte dysfunction
Defect: AR defective integrin (LFA1, CD18) > impaired chemotaxis
Presentation: Recurrent bacterial skin and mucosal infxns, no pus formation, impaired wound healing, delayed sep of umb cord, increased PMNs (not marginated) but none at site of infxn.

Question 12

Chediak Higashi

Answer 12

Phagocyte dysfunction:
Defect: AR defect (LYST gene) in microtubule phagolysosome fusion
Presentation: partial albinism, recurrent pyogenic infxn by staph and strep, peripheral neuropathy, progressive neurodegen, infiltrative lymphohistiocytosis (diagnostic); will see giant granules in PMNs and platelets, pancytopenia, mild coag defects

Question 13

Chronic Granulomatous Disease

Answer 13

Phagocyte dysfunction
Defect: X-linked recessive defect in NADPH oxidase > decreased reactive oxygen species and absent resp burst in PMNs
Presentation: Recurrent infxns with catalase+ organisms (PLACESS: Pseudomonas, Listeria, Aspergillus, Candida, Ecoli, Staph aureus, Serratia); abnormal dihydrodamine test, negative nitroblue tetrazolium dye test.