Immunodeficiency: NAME THE GENE DEFECT

Question 1

HyperIgM Syndrome: defect and mode of inheritance

Answer 1

XR, CD40L/CD40

Question 2

X linked agammaglobulinemia (Bruton’s hypogammaglobulinemia): defect and mode of inheritance

Answer 2

XR, BTK gene
presents with non-infectious granulomas, increase risk for heme malignancies, may present with helicobacter bilis associated PG

Question 3

SCID severe combined immuodef

Answer 3

XR and AR
XR – IL2RG
AR – ADA, JAK3
May have GVHD-like presentation. + failure to thrive. no palpable lymph nodes

Question 4

CID (omenn syndrome)

Answer 4

AR; RAG1/2***, Artemis, IL-7 R Alpha gene. presents with erythroderma and alopecia. May also note LAD and hepatosplenomegaly.

Question 5

Wiskott-Aldrich

Answer 5

XR, WAS gene

petechiae, epistaxis, + atopy (food allergies, asthma, urticaria), high levels of IgA/D/E, increased risk of NHL

Question 6

Ataxia-Telangiectasia

Answer 6

AR, ATM gene
truncal ataxia>peripheral ataxia, sensitivity to ionizing radiation, increase risk of malignancies, female heterozygotes at increased risk for breast cancer

Question 7

Chronic Mucocutaneous Candidiasis

Answer 7

AD or AR, impaired IL-17 role, defect in STAT1**, CARD9, IL-17RA, IL-17F, CLEC7A, TRAF3IP2
presents with mucocutaneous candidiasis and deep dermatophytosis

Question 8

APECED (autoimmune polyendocrinopathy-candidiasis–ectodermal dystrophy)

Answer 8

AR; AIRE gene

Question 9

HyperIgE (Job syndrome)

Answer 9

AR, AD; Stat 3 (AD) or DOCK8 (AR)
STAT3 - 30% of abscesses are COLD; coarse facial features (broad nasal bride, big nose); retained primary teeth w/problematic secondary teeth
DOCK8 - no dysmorphic cutaneous features

Question 10

WHIM (warts, hypogamm, infection, myelokathexis)

Answer 10

AD; CXCR4

presents with extensive HPV warts and myelokathexis (peripheral neutropenia with retention of PMNs in bone marrow)

Question 11

HED (hypohidrotic ectodermal dysplasia)

Answer 11

XR; NEMO gene (akin to IP)

presents with conical incisors, decrease/absence of sweat glands and hair follicles

Question 12

LAD leukocyte adhesion deficiency

Answer 12

AR; ITGB2 defect
presents with pyoderma, bacterial ulcerations mimicking PG, delayed separation of umbilical cord, poor wound healing, periodontitis

Question 13

Chronic Granulomatous Disease

Answer 13

XR and AR; defect in CYBB and CYBA; NADPH oxidase defect affects phagocytes; presents with pneumonia of catalase + organisms, noninfectious granulomas, gingivitis/stomatitis, hepatosplenomegaly, cervical LAD, female carriers may have increased risk of lupus***; can make diagnosis with nitro blue tetrazolium test **

Question 14

Chediak Higashi

Answer 14

AR; LYST gene
presents with pigmentary dilution (silvery hair and hypoPIgmented skin), hypERpigmentation in acral sites, pyoderma, bacterial ulcerations mimicking PG, accelerated lymphohistiocytic phase and giant granules or melanosomes in WBCs or melanocytes

Question 15

Griscelli Syndrome

Answer 15

GS1 - MYO5A
GS2 - Rab27a *** main one listed in text books
presents with pigmentary dilution (silvery hair and hypoPIgmented skin), accelerated lymphohistiocytic phase. neurologic deterioration in MYO5A type.

Question 16

what is the defect in digeorge syndrome? (Hint: what chromosome?) This falls under the category of Catch-22 diseases

Answer 16

chromosome 22

Question 17

IgA deficiency

Answer 17

IGAD1 mutation; recurrent sinopulmonary bacterial infx and giardia gastroenteritis; presents with eczematous dermatitis.

**most COMMON immunoglobulin deficiency

Question 18

CVID

Answer 18

mutations in the following: ICOS, CD19, CD20, CD21, CD81, LRBA1, TACI, BAFFR, NFKB2, IL21, and PRKCD
may present with bacterial infx, noninfectious granulomas, hypogammaglobulinemia, and increase risk of heme malignancies

Question 19

IPEX (immunodeficiency, polyendocrinopathy, and X linked)

Answer 19

FOXP3; presents as eczematous dermatitis, severe diarrhea, T1DM, hypothyroidism, and autoimmune hemolytic anemia

Question 20

EDV (epidermodysplasia verruciformis)

Answer 20

EVER1/2 defect; common infx: HPV 5, 8, and more; warts may transform to malignancies

Question 21

Monomac

Answer 21

GATA2 defect; common infx: HPV, atypical mycobacteria, deep fungal infx
may present with pulmonary alveolar proteinosis, and increased risk of heme malignancies