Capstone: Immunodeficiencies & Metabolic Disorders

Front 1

hereditary angioedema.

ACE inhibitors are contraindicated with this deficiency

Back 1

C1 esterase inhibitor deficiency

Front 2

Causes severe, recurrent pyogenic sinus and respiratory tract infections;

increases susceptibility to type III hypersensitivity rxns

Back 2

C3 deficiency

Front 3

causes recurrent Neisseria bacteremia

Back 3

C5-C8 (MAC) deficiencies

Front 4

causes complement-mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria (PNH)

Back 4

DAF (GPI anchored enzyme) deficiency

(decay accelerating factor)

Front 5

anaphylaxis, allergic & atopic disorders are all what type hypersensitivity?

Back 5

type 1: immediate, anaphylactic, atopic

What tests type 1 disorders?

Hint 5

scratch test and radioimmunosorbent assay

Front 6

Erythroblastosis fetalis, rheumatic fever, goodpasture's syndrome, bullous & pemphigus vulgaris, Grave's disease and myasthenia gravis are all what type hypersensitivity disorders?

Back 6

type 2: disease tends to be specific to tissue or site where antigen is found

What tests type 2?

Hint 6

direct and indirect coomb's

Front 7

SLE, RA, PAD, serum sickness, arthus rxn, hypersensitivity pneumonitis are all what type hypersensitivity disorders?

Back 7

type 3: can be associated w/ vasculitis and systemic manifestations

What tests type 3?

Hint 7

immunofluorescent staining

Front 8

Type 1 DM, MS, GBS, Hashimoto's, Graft-vs-host disease, PPD, and contact dermatitis are all what type hypersensitivity rxns?

Back 8

type 4: response is delayed and does NOT involve antibodies

what tests type 4?

Hint 8

patch test (i.e. ppd)

Front 9

anti-desmoglein

Back 9

pemphigus vulgaris

Front 10

antimicrosomal

Back 10

hashimoto's thryogiditis

Front 11

antithryoglobulin

Back 11

hashimoto's thyroiditis

Front 12

anti-RNP

Back 12

MCTD

Front 13

anti-smooth muscle

Back 13

autoimmune hepatitis

Front 14

anti-glutamate decarboxylase

Back 14

type 1 DM

Front 15

antimitochondrial

Back 15

Primary biliary cirrhosis

Front 16

antiendomysial

Back 16

celiac disease

Front 17

recurrent bacterial infections after 6 months (decrease in maternal IgG) due to opsonization defect.

Absence of thymic shadow

Back 17

Bruton's agammaglobinemia
X-linked recessive

Defect in BTK, a tyrosine kinase--> blocks pro-B cells from forming pre-B cells

Hint 17

Labs:
Normal pro-B
decreased maturation, number of B cells, immunoglobulins of all classes

Front 18

severe pyogenic infections early in life

Back 18

Hyper-IgM syndrome

Defect in CD40L on Th cells causing inability to class switch

Hint 18

Labs:
Increased IgM
Decreased IgG, IgA, IgE

Front 19

sinus and lung infections, milk allergies and diarrhea
Anaphylaxis on exposure to blood products w/ IgA

Back 19

Selective Ig deficiency

defect in isotype switching --> deficiency in specific class of immunoglobulins

Hint 19

IgA deficiency most common

Failure to mature into plasma cells. Decreased secretory IgA

Front 20

Can be acquired in 20s-30s; risk of autoimmune disease, lymphoma, sinopulmonary infections

Back 20

CVID

Defect in B-cell maturation; many causes

Hint 20

Normal number of B cells; decreased plasma cells, immunoglobulins

Front 21

Tetany (hypocalcemia), recurrent viral/fungal infections, congenital heart and great vessel defects

Back 21

Thymic aplasia (DiGeorge Syndrome)

22q11 deletion; failure to develop 3rd and 4th pharyngeal pouches

Hint 21

Thymus and parathyroids fail to develop--< decreased T cells, decreased PTH, decreased Ca++

Absent of thymic shadow on CXR

Front 22

disseminated mycobacterial infections

Back 22

IL-12 receptor deficiency

Decrease in TH1 response

Hint 22

Lab:
decreased IFN-gamma

Front 23

coarse facies, cold staphylococcus abscesses, retained primary teeth, increased IgE, Dermatologic problems (eczema)

Back 23

Hyper-IgE syndrome (Job's syndrome)

Th cells fail to produce IFN-gamma--> inability of neutrophils to repsond to chemotactic stimuli

Hint 23

increased IgE

Front 24

candida albicans infections of skin and mucous membranes

Back 24

Chronic mucocutaneous candidaisis:

T-cell dysfunction

Front 25

recurrent viral, bacterial, fungal and protozoal infections due to both B and T cell deficiency. Absence of thymic shadow, germinal centers, and B cells.

Treatment: bone marrow transplant

Back 25

SCID

Several types: defect IL-2 receptor (most common, x-linked),
ADA deficiency
Failure to synthesize MHC II antigens

Hint 25

decreased IL-2R
Increased adenine
decreased dNTPs, DNA synthesis

Front 26

Triad: cerebellar defects (ataxia), spider angiomas (telangectasia), IgA deficiency

Back 26

Ataxia-telangectiasia

Defects in ATM gene, which codes for DNA repair enzymes

Hint 26

IgA deficiency

Front 27

Triad: Thrombocytopenic purpura, Infections, Eczema

Back 27

Wiskott-Aldrich syndrome

X-linked recessive defect. Progressive deletion of B and T cells

Hint 27

increased IgE, IgA
Decreased IgM

Front 28

recurrent bacterial infections, absent pus formation, delayed separation of umbilicus

Back 28

LAD Type 1

Defect in LFA-1 antigen (CD18) protein on phagocytes

Hint 28

neutrophilia

Front 29

recurrent pyogenic infection by staph and strept; partial albinism, peripheral neuropathy

Back 29

Chediak-Higashi syndrome

autosomal recessive; defect in lysosomal regulator trafficing gene (LYST).

Microtubule dysfunction in phago-lysosome fusion

Front 30

Increased susceptibility to catalase-positive organisms (S. aureus, E. coli, Aspergillus)

Back 30

Chronic granulomatous Disease

Lack of NADPH oxidase --> decrease reactive oxygen species and absent respiratory burst in neutorphils

Hint 30

negative nitroblue tetrazolium dye reduction test

Front 31

abl (oncogene)

Back 31

CML

Hint 31

tyrosine kinase

Front 32

c-myc (oncogene)

Back 32

Burkitt's lymphoma

Hint 32

transcription factor

Front 33

bcl-2 (oncogene)

Back 33

follicular and undifferentiated lymphomas

Hint 33

anti-apoptotic molecule

Front 34

erb-B2 (oncogene)

Back 34

Breast
Ovarian
Gastric carcinomas

Hint 34

tyrosine kinase

Front 35

ras (oncogene)

Back 35

Colon carcinoma

Hint 35

GTPase

Front 36

L-myc (oncogene)

Back 36

Lung Tumor

Hint 36

Transcription factor

Front 37

N-myc (oncogene)

Back 37

Neuroblastoma

Hint 37

transcription factor

Front 38

ret (oncogene)

Back 38

Multiple Endocrine Neoplasia (MEN) types IIA and IIB

Hint 38

Tyrosine Kinase

Front 39

c-kit (oncogene)

Back 39

Gastrointestinal stromal tumor (GIST)

Hint 39

Cytokine receptor

Front 40

Rb (tumor suppressor gene)

Back 40

Retinoblastoma, osteosarcoma

Hint 40

Rb gene product blocks G1--> S phase of cell cycle

Front 41

p53 (tumor suppressor gene)

Back 41

Most cancers
Li-Fraumeni syndrome

Hint 41

p53 gene product blocks G1--> S phase of the cell cycle

Front 42

BRCA1 (tumor suppressor gene)

Back 42

Breast and Ovarian cancer

Hint 42

DNA repair protein

Front 43

BRCA2 (tumor suppressor gene)

Back 43

Breast Cancer

Hint 43

DNA repair protein

Front 44

p16 (tumor suppressor gene)

Back 44

Melanoma

Front 45

APC (tumor suppressor gene)

Back 45

Colorectal cancer (associated w/ FAP)

Front 46

WT1 (tumor suppressor gene)

Back 46

Wilm's Tumor

Front 47

NF1 (tumor suppressor gene)

Back 47

Neurofibromatosis type 1

Front 48

NF2 (tumor suppressor gene)

Back 48

Neurofibromatosis type 2

Front 49

DPC (tumor suppressor gene)

Back 49

Pancreatic Cancer

Hint 49

DPC: Deleted in Pancreatic Cancer

Front 50

DCC (tumor suppressor gene)

Back 50

Colon Cancer

Hint 50

DCC: deleted in Colon Cancer

Front 51

Name the disease:
mental retardation
flat facies
epicanthal folds
simian crease

Back 51

Down Syndrome (Trisomy 21)

Hint 51

associated w/ increased risk of ALL and Alzheimer's

quad screen: increased B-hCG, inhibin A
Decreased: a-FP, estriol

Front 52

Name the disease:
severe mental retardation
micrognathia
low-set ears
clenched hands

Back 52

Edward's Syndrome (18)

Hint 52

quad screen: all decreased

Front 53

Name the disease:
severe mental retardation
cleft lip/palate
holoprosencephaly
polydactyly

Back 53

Patau's syndrome (13)

Hint 53

quad screen is normal

Front 54

Name the disease:
MR
growth retardation
seizures
fair skin
musty body odor

Back 54

PKU (AR)

Hint 54

Rx: decrease phenylalanine and increase tyrosine

Front 55

Name the disease:
dark connective tissue
brown pigmented sclera
black urine
arthralgias

Back 55

Alkaptonuria (ochronosis)

Hint 55

Congenital deficiency of homogentisic acid oxidase

Front 56

What causes albinism?

Back 56

deficiency of
1) tyrosinase
2) defective tyrosine transporters

Front 57

Name the disease:
MR
osteoporosis
tall stature
kyphosis
lens subluxation
atherosclerosis
joint restriction

Back 57

Homocystinuria

Hint 57

3 forms:
1) Cystathionine synthase deficiency
2) decrease affinity of cystathionine synthase for pyridoxal phosphate
3) homocysteine methyltransferase deficiency

Front 58

Cystinuria is a renal tubular amino acid transporter defect for what 4 amino acids

Back 58

cysteine
orthinine
lysine
arginine
"CORK"

how can you treat the precipitation of cystine kidney stones?

Hint 58

acetazolamide to alkalinize the urine

Front 59

Maple syrup urine disease is a defect of blocked degradation of what?

Back 59

branched amino acids
Ile, Leu, Val due to decrease alpha-ketoacid dehydrogenase

Causes increased ketoacids in the blood (esp. Leu)

Front 60

What disease causes tryptophan excretion in urine and decreased absorption from gut leading to pellagra?

Back 60

Hartnup disease (AR) - defect in neutral amino acid transporter on renal and intestinal epithelial cells

Front 61

Name the disease:
severe fasting hypoglycemia (seizures)
Increased glycogen in liver
Increased blood lactate
hepatomegaly

Back 61

Von Gierke's disease
Type 1 Glycogen storage dz

What is the deficient enzyme?

Hint 61

Glucose-6-Phosphatase

Front 62

Name the disease:
Cardiomegaly
Systemic findings
early death

Back 62

Pompe's Dz
Type II Glycogen storage Dz

Deficient enzyme?

Hint 62

lysosomal alpha-1,4-glucosdiase (acid maltase)

Front 63

Type III glycogen storage disease is called what?

Back 63

Cori's Dz - milder form of type I with normal lactate levels

Enzyme deficiency?

Hint 63

Debranching enzyme
(alpha-1,6 glucosidase)

**gluconeogenesis is intact**

Front 64

Name the disease:
Increase in glycogen in muscle, but cannot break it down, leading ot painful muscle cramps, myoglobinuria w/ strenuous exercise

no Hepatomeagaly

Back 64

Type V Glycogen storage Dz: McArdle's Disease

Enzyme deficiency?

Hint 64

Skeletal muscle glycogen phosphorylase

Front 65

Name the disease:
Peripheral neuropahty of hands/feet
angiokeratomas
cardiovascal & renal disease

Back 65

Fabry's Dz

What is the deficient enzyme, accumulated substrate and inheritance pattern?

Hint 65

DE: alpha-galactosidase A

AS: Ceramide trihexose

IN: XR

Front 66

Name the disease:
Hepatosplenomegaly
aseptic necrosis of femur
bone crisis
Macrophages that look like crumpled tissue paper

Back 66

Gaucher's Dz

What is the deficient enzyme, accumulated substrate and inheritance pattern?

Hint 66

DE: Glucocerebrosidase

AS: Glucocerebroside

IN: AR

Front 67

Name the disease:
Progressive neurodegeneration
Hepatosplenomegaly
Cherry-red spot on macula
foam cells

Back 67

Niemann-Pick Disease

What is the deficient enzyme, accumulated substrate and inheritance pattern?

Hint 67

DE: Sphingomyelinase

AS: Sphingomyelin

IN: AR

Front 68

Name the disease:
Neurodegeneration
Developmental delay
Cherry-red spot on macula
Lysosomes w/ onion skin
NO HSM

Back 68

Tay-Sachs Dz

What is the deficient enzyme, accumulated substrate and inheritance pattern?

Hint 68

DE: Hexosamindase A

AS: Gm2 Ganglioside

IN: AR

Front 69

Name the disease:
Peripheral neuropathy
Developmental delay
Optic atrophy
Globoid cells

Back 69

Krabbe's Dz

What is the deficient enzyme, accumulated substrate and inheritance pattern?

Hint 69

DE: B-galactocerebrosidase

AS: Galactocerebroside

IN: AR

Front 70

Name the disease:
Central and peripheral demyelination with ataxia
dementia

Back 70

metachromic leukodystrophy

What is the deficient enzyme, accumulated substrate and inheritance pattern?

Hint 70

DE: Arylsulfatase A

AS: Cerebroside sulfate

IN: AR

Front 71

Name the disease:
Developmental delay
Gargoylism
Airway obstruction
Corneal Clouding
HSMM
Dwarfism
Cardiomyopathy/vavular defects

Back 71

Hurler's Syndrome

What is the deficient enzyme, accumulated substrate and inheritance pattern?

Hint 71

DE: alpha-L-iduronidase

AS: Heparin sulfate, dermatan sulfate

IN: AR

Front 72

Name the disease:
Mild Hurler's
aggressive behavior
No corneal clouding

Back 72

Hunter's syndrome

What is the deficient enzyme, accumulated substrate and inheritance pattern?

Hint 72

DE: Iduronate sulfatase

AS: Heparan sulfate, dermatan sulfate

IN: XR

Front 73

Name the disease:
pancreatitis
HSM
eruptive/pruritix xantomas
Increased TG, cholesterol

Back 73

I-hyper-chylomicronemia

Increased chylomicrons --> increased TG, cholesterol in blood

What enzyme deficiency?

Hint 73

Lipoprotein Lipase deficiency or altered apolipoprotein C-II

Front 74

Name the disease:
accelerated atherosclerosis
tendon (Achilles) xanthomas
corneal arcus

Back 74

IIa-Familial hypercholesterolemia

Increased LDL --> increased cholesterol in blood

What deficiency?

Hint 74

absent or decreased LDL receptors

Front 75

Name the disease:
pancreatitis
Increased TG

Back 75

IV Hypertriglyceridemia

Hepatic overproduction of what?

Hint 75

VLDL