Inherited Immunodeficiencies Flashcards
X-linked (Brutons) agammaglobulinemia
Defect
B Cell Disorder
Defect in BTK an adenosine kinase gene - leading to failure of bone marrow pre-B cells to mature
X-linked (Brutons) agammaglobulinemia
Presentation
Lab: Absent B cells, Dec Ig of all classes
Clinical: absent/scanty lymph nodes and tonsils, recurrent bacterial (encapsulated) enteroviral (polio and coxsackie) and giardia infections (AFTER 6 months)
Selective IgA deficiency
Defect
B Cell Disorder
Unknown but is most common primary immunodeficiency
Selective IgA deficiency
Presentation
Lab: Dec IgA w/ normal IgG,IgM levels
Clinical: Inc susceptibility to giardiasis and anaphylaxis to IgA containing products, most asymptomatic; but can see inc gi infections, autoimmune, atopy, and some association with celiacs
CVID
Defect
B Cell Disorder
Defect in B-cell DIFERENTIATION (not maturation like brutons)
CVID
Presentation
Lab: Dec plasma cells, Dec immunoglobulins
Clinical: usually presents after 2 or later; inc risk of autoimmune disease, lymphoma, bronchiectasis, and sinopulmonary infections (inc risk for bacterial, enterovirus and giardia again)
Thymic Aplasia (DiGeorge Syndrome) (Defect)
T cell Disorder
22q11 deletion; failure to develop 3rd and 4th pharyngeal pouches –> absent thymus and parathyroids
Thymic Aplasia (DiGeorge Syndrome) (Presentation)
Lab: Dec T cells; Possibly Dec PTH and Dec Ca
Clinical: Recurrent VIRAL and FUNGAL infections (also Protozoan and INTRAcellular bacteria); conotruncal abnormalities (tetrology, and tuncus arteriosus), Hypocalcemia if Parathyroids absent
IL-12 Receptor Deficiency
Defect
T cell disorder
Dec Th1 Response Autosomal recessive
IL-12 Receptor Deficiency
Presentation
Lab: Dec IFN-Y
Clincial: disseminated MYCOBACTERIAL and FUNGAL infections, may present after administration of BCG vaccine
Job syndrome (hyper IgE syndrome) (Defect)
T Cell disorder
Deficiency of Th17 Cells due to STAT 3 mutation
Impaired recruitment of neutrophils to infection sites
Job syndrome (hyper IgE syndrome) (Presentation)
Lab: Inc IgE, Dec IFN-y, Inc Eosinophils
Clinical: FATED; course Facies, cold (noninflamed) staph Abscesses, retained primary Teeth, Inc IgE, Dermatologic problems (eczema). Also bone fractures from relatively minor trauma
Chronic Mucocutaneous Candidiasis
Defect
T Cell Disorder
Many causes
Chronic Mucocutaneous Candidiasis
Presentation
Labs: Absent in vitro T cell proliferation in response to candida antigens; absent cutaneous reaction to candida antigens
Clinical: non invasive candida infections of skin and mucosal membranes
SCID
Defect
B and T Cell Disorders
MC- Defective IL-2R gamma chain; x linked
Adenosine deaminase deficiency (autosomal recessive)
MHC class II defect (autosomal recessive)
SCID
Presentation
Lab: Dec T cell receptor excision circles; absence of thymic shadow, germinal centers and t cells (-on flow cytometry)
Clinical: failure to thrive, chronic diarrhea, thrush, recurrent viral, bacterial, fungal, and protozoal infections. need to avoid live vacciens and give prophy and ivig; bone marrow transplant is curative (no rejection concern)
Ataxia Telangiectasia
Defect
B and T Cell Disorders
Defect in ATM gene; failure to repair DNA double strand breaks leading to cell cycle arrest
Ataxia Telangiectasia
Presentation
Lab: Inc AFP, Dec IgA,G,E, lymphopenia, cerebellar atrophy,
Clinical: inc risk of lymphoma and leukemia; TRIAD Cerebellar defects (Ataxia), spider Angiomas, igA deficiency (sinopulmonary infections)
Hyper IgM Syndrome
Defect
B and T Cell Disorders Most commonly due to defective CD40L on Th cells-> class switching defect X linked recessive (could also be a cd40 deficiency on B cells which is rare and auto rec)
Hyper IgM Syndrome
Presentation
Lab: normal or Inc IgM, Very Dec IgG,A,E, Failure to make germinal centers
Clinical; severe pyogenic infections early in life; oportunistic infection with PNeumocystis, crypto, and CMV
Wiskott Aldrich Syndrome
Defect
B and T Cell Disorders
Mutation in WASp Gene; leukocytes and platelets unable to reorganize actin cytoskeleton causing defective antigen presentation
x linked recessive
Wiskott Aldrich Syndrome
Presentation
Lab: Dec to normal IgG, IgM, Inc IgE, IgA, fewer and smaller platelets
Clinical: WATER (Wiskott-Aldrich) Thrombocytopenia, Exczema, Recurrent pyogenic infections (encapsul), bleeding is a common cause of death, inc risk of autoimmune disease and malignancy
Leukocyte adhesion deficiency (type 1)
Defect
Phagocyte Dysfunction
Defect in LFA-1 integrin (CD-18) on phagocytes impaired migration and chemotaxis
Autosomal recessive
Leukocyte adhesion deficiency (type 1)
Presentation
Lab: inc neutrophils, absence of neutrophils at INFECTION SITES
Clinical: Recurrent skin and mucosal bacterial infections, absent pus, impaired wound healing (>30 days), separation of umbilical cord
Chediak-Higashi Syndrome
Defect
Phagocyte Dysfunction
Defect in lysosomal trafficking regulator gene LYST
microtubule dysfunction in phagosome lysosome fusion
autosomal recessive
Chediak-Higashi Syndrome
Presentation
Lab: giant granules in platelets and granulocytes, pancytopenia, mild coagulation defects (due to abnormal granules in platelets)
Clinical: Recurrent pyogenic infections by staph and strep, partial albinism, periph neuropathy (failure to transport nutrients), progressive neurodegeneration, infiltrative lymphohistiocytosis
Chronic Granulomatous Disease
Defect
Phagocyte Dysfunction
Defect of NADPH oxidase (dec reactive oxygen species and dec resp burst in neutrophils)
x linked recessive
Chronic Granulomatous Disease
Presentation
Lab: abnormal dihydrorhodamine test (dec green fluorescence), Fails to turn blue on nitroblue tetrazolium dye test
Clinical: inc susceptibility to catalase + organisms
