Drx 1: Foundations Lectures 18 And 20

Front 1

Mode of Inheritance of Hereditary Hemochromatosis (HHC)

Back 1

AR

Front 2

An individual with two mutations in one allele of the HFE gene (H63D and C282Y) is termed a ___________ and (does/doesn't)? have hemochromatosis.

Back 2

An individual with two mutations in one allele of the HFE gene (H63D and C282Y) is termed a compound heterozygote and doesn't have hemochromatosis.

Front 3

Only 20% of individuals with two mutated HFE genes have phenotypic hemochromatosis. This is termed:

Back 3

Incomplete penetrance

Front 4

Which of the following is NOT a symptom of HHC?
A. Fatigue
B. Joint Pain
C. Infertility/Low libido
D. Cardiomyopathy
E. Bronze diabetes: diabetes, cirrhosis, increased pigmentation
F. hepatocellular carcinoma
G. early-onset Alzheimer's

Back 4

G

Front 5

Diagnosis of HHC should involve
A) Serum ferritin
B) Transferrin iron saturation percentage
C) Serum hemosiderin
D) Genotyping
E) A + B
F) A + B + D
G) All of the above

Back 5

E

Front 6

Treatment of HHC involves
A) Serial phlebotomy
B) Deferoxamine, an iron-chelating agent
C) A and B

Back 6

C

Front 7

Mode of inheritance of Marfan Syndrome

Back 7

AD

Front 8

Fibrillin 1 is the gene mutated in Marfan syndrome; its product, fibrillin:
A) Is an important constituent in the basement membrane
B) Primarily binds collagen fibrils
C) Forms part of the epithelial reticulum in some organs
D) Stabilizes elastin filaments

Back 8

D

Front 9

Which of the following concerning prevalences and penetrance is INCORRECT?
A) HHC: 1:220
B) Marfan Sx 1:5000
C) HHC: largely dependent on modifier genes
D) Marfan Sx: more common in men

Back 9

D

Front 10

Which of the following IS NOT typical of Marfan syndrome?
A) Arachnodactyly (long fingers)
B) Hollow chest
C) Great flexibility
D) Receding jaw
E) Broad shoulders
F) Dislocation of the lens, cataracts, glaucoma
G) Aortic dissection
H) Mitral valve prolapse

Back 10

E

Front 11

True or false: Marfan syndrome presents variably within a family.

Back 11

True;
A good example of variable expressivity

Front 12

A patient presents with skeletal and dental features that make you suspicious of Marfan's syndrome. However, there is no family history of cardiac problems and an extensive family history of hip problems. What might this be?

Back 12

Congenital contractural arachnodactyly, caused by a mutation in fibrillin 2.

Front 13

What is the mode of inheritance of Familial Hypercholesterolemia due to LDL-R mutation?

Back 13

Wellll... mostly AD, but homozygotes have a more extreme form. Hence, the inheritance is, strictly speaking, codominant.

Front 14

The prevalence of LDL-R mutations is approximately:
A) 1:10
B) 1:25
C) 1:500
D) 1:2,500
E) 1:10,000

Back 14

C

Front 15

Which of the following IS NOT a common result of LDL-R mutations?
A) High plasma cholesterol (>300 mg/cc)
B) High serum LDL (>200)
C) High TGs
D) Xanthomas
E) Chest pain (angina)
F) Cirrhosis
G) Obesity

Back 15

F

Front 16

Which of the following mutations does not cause familiar hypercholesterolemia?
A) LDL-R
B) 5'-lipoxygenase
C) Apolipoprotein-B
D) LDL-R adaptor
E) PCSK9

Back 16

B
5'Lipoxygenase mutation increases leukotriene production

Front 17

Which of the following is incorrect?
A) PCSK9 - degrades LDL-R, AD gain of function --> hypercholesterolemia
B) 5'-lipoxygenase - makes extra leukotrienes, 6% prevalence
C) Apolipoprotein-B - Ligand for LDL-R, AD-inherited hypercholesterolemia
D) LDL-R adaptor - affects internalization of LDL-R, fairly common, AD inheritance
E) PCSK9 - 2% of African Americans have an AD LOF, leading to lower serum cholesterol

Back 17

D - LDL-R adaptor inheritance is AR and rare

Front 18

The Virchow triad for thrombosis includes all the following except:
A) Endothelial injury
B) Inflammatory response
C) Abnormal blood flow
D) Hypercoagulability

Back 18

B

Front 19

Factor V Leiden, in activated form (Va) is resistant to _______ in 1-15% of different populations:
A) Antithrombin III
B) Protein C
C) Protein S
D) Prothrombin

Back 19

B

Front 20

Which ONE OR MORE of the following is a coagulant?
A) Antithrombin III
B) Protein C
C) Protein S
D) Prothrombin

Back 20

D

Front 21

Which of the following is not a cause of hypercoagulability and DVT?
A) Factor V mutation
B) Prothrombin mutation
C) Antithrombin III deficiency
D) Protein C deficiency
E) Protein S deficiency
F) Homocysteine mutation

Back 21

F

Front 22

Which of the following IS NOT a secondary cause of hypercoagulability (and DVT)?
A) Pregnancy (hyperestrogen)
B) Smoking
C) Oral contraceptive use
D) Obesity
E) Alcoholism
F) Antiphospholipid antibody syndrome (present in 1/5 patients with a recent stroke)
G) Heparin-induced thrombocytopenia

Back 22

E

Front 23

Mode of inheritance of Hemophilia A

Back 23

X-linked recessive

Front 24

Mode of inheritance of Hemophilia B

Back 24

X-linked recessive

Front 25

Mutated gene in hemophilia A

Back 25

Factor VIII

Front 26

Mutated gene in hemophilia B

Back 26

Factor X (Christmas factor)

Front 27

Incidence of hemophilia A in males is closest to:
A) 1:100
B) 1:1,000
C) 1:10,000
D) 1:100,000

Back 27

C;
1:10,000

Front 28

Approximately what percentage of hemophilia cases are caused by Christmas Disease?
A) 2%
B) 8%
C) 15%
D) 25%

Back 28

C

Front 29

Define hemizygous.

Back 29

Having only one allele at a given locus; ex. human males with X or Y genes, say, for hemophilia A

Front 30

Describe the clinical significance of 'unfavorable lyonization' in Hemophilia A

Back 30

Some females might get unlucky and get X-silencing (lyonization) on the chromosome expressing a mutated factor VIII gene, causing them to have excessive bleeding.

Front 31

Which ONE OR MORE of the following are symptoms typical of Hemophilia A?
A) chronic joint pain (arthropathy)
B) muscle pain and atrophy
C) hepatosplenomegaly
D) Peripheral nerve lesions, esp. in arms and legs
E) Hemorrhaging in various organs

Back 31

A, B, D and E

Front 32

You find decreased Factor VIIIc in a patient's serum. What disease or diseases might you be observing?

Back 32

There are two good possibilities, Hemophilia A and Von Willebrand Disease. vWF stabilizes Factor VIII leading to decreased levels when it is mutated.

Front 33

Which of Partial Thromboplastin Time (PPT) and Prothrombin Time (PT) is extended in Hemophilia A?

Back 33

PPT;
It tests the extrinsic and intrinsic pathways; PT just tests the extrinsic (using thromboplastin to initiate that pathway). Factor VIII is only essential to the intrinsic pathway.

Front 34

Which ONE OR MORE of the following are normal findings for Hemophilia A?
A) Prolonged PPT
B) Decreased factor VIIIc
C) Normal PT
D) Normal bleeding time
E) Normal thrombin time
F) Normal platelet count
[G) Normal Factor VIIIvW ] <-- apparently true

Back 34

All of the above

Thrombin Time (TT or TCT) is thrombin clotting time and tests heparin and fibrinogen fxn.

Front 35

There are _ classes of severity of hemophilia.

Back 35

3;
1st affects newborns and bleeding is spontaneous
2nd affects infants and bleeding accompanies trauma
3rd is less severe and usually accompanies more severe trauma or surgery

Front 36

Compare the frequency of von Willebrand disease to that of Hemophilia A:
A) Equally common
B) 1/10th as common
C) 1/100th as common
D) 10x as common
E) 100x as common

Back 36

E;
vW: 1%
Hemophilia A: ~1/7,500 males

Front 37

Clinical manifestations of Von Willebrand Disease include all the following EXCEPT:
A) Spontaneous bleeding from mucous membranes
B) Excessive bleeding from wounds
C) Joint Pain
D) Menorrhagia (Heavy periods)
E) Prolonged bleeding time but normal platelet count

Back 37

C

Front 38

Ristocetin is an out-of-use antibiotic which is now used to test the activity of vWF in the ristocetin aggregation test. Give a simple reason why this test, while good, is still not always enough for a complete diagnosis.

Back 38

vW disease is highly variable.

Front 39

Asthma is an example of which ONE OR MORE of the following?
A) Type 1 Hypersensitivity
B) Type 2 Hypersensitivity
C) Type 3 Hypersensitivity
D) Atopy

Back 39

A and D (they're synonyms)

Front 40

Approximately how many genes have been associated with asthma?
A) 1
B) 5
C) 25
D) 200

Back 40

C

Front 41

Environmental factors affecting asthma include which of the following?
A) Allergens
B) Air pollutants
C) Viral upper-respiratory infections
D) Emotional Stress
E) Exercise
F) Humidity

Back 41

All of the Above

Front 42

Approximately what is the incidence of asthma?
A) .1%
B) 1%
C) 7%
D) 15%

Back 42

C

Front 43

Organs rich in which cell type are prone to damage in lysosomal storage diseases?

Back 43

Macrophages-
Spleen, liver, lymph nodes

Front 44

Name three kinds of molecules derived from sphingosine.

Back 44

Sphingomyelin, Cerebrosides and Gangliosides

Front 45

Tay-Sachs disease is caused by an enzyme deficiency in ____________ causing an accumulation of ______________.

Back 45

Tay-Sachs disease is caused by an enzyme deficiency in Hexosaminidase A causing an accumulation of GM2 Ganglioside.

Front 46

What is the EM appearance of neuronic vacuoles (distended lysosomes) in Tay-Sachs disease?

Back 46

They have whorled inclusions, making them look like onion skin.

Front 47

Which of the following IS NOT a clinical manifestation of Tay-Sachs disease?
A) Motor and mental deterioration
B) Muscle flaccidity
C) Obtundation
D) Blindness
E) Xanthomas
F) Cherry red spot in retina
E) Death by age 3

Back 47

E;

That's an occassional symptom of Niemann-Pick disease

Front 48

What is the mode of inheritance of lysosomal storage disorders?

Back 48

AR

Front 49

Niemann-Pick disease might be termed _____________ deficiency, after the enzyme which cannot break down _____________ and _____________.

Back 49

Niemann-Pick disease might be termed Sphingomyelinase deficiency, after the enzyme which cannot break down Sphingomyelin and Cholesterol.

Front 50

Match the Type of Niemann-Pick Disease to the appropriate information:
75-80% of cases // CNS involvement // no CNS involvement

A // B

Back 50

A - CNS involvement, 75-80% of cases
B - no CNS involvement

Front 51

In Niemann-Pick disease the cell type of ____________ contains cytoplasm that looks _____ and contains, upon EM, numerous ______ bodies.

Back 51

In Niemann-Pick disease the cell type of macrophages contains cytoplams that looks foamy and contains, upon EM, numerous zebra bodies (or concentric 'myelin' figures).

Front 52

Are any of the following NOT symptoms of Niemann-Pick Disease (either type)?
-Protuberant Abdomen
-Splenomegaly up to 10x normal
-Hepatomegaly
-Failure to Thrive
-Progressive deterioration of motor function
-Skin xanthomas
-Cherry red spot on retina
-Early death (age 3)

Back 52

All are symptoms

Cherry red spot is more common in Tay Sachs.(only 30-50% of Niemann-Pick patients)

Front 53

Gaucher's disease might be termed ____________ deficiency if it were named for the enzyme which is deficient, which breaks down ___________ in lysosomes.

Back 53

Gaucher's disease might be termed glucocerebrosidase deficiency if it were named for the enzyme which is deficient, which breaks down glucocerebrosides in lysosomes.

Front 54

Match the molecule with the disease:
A. Sphingomyelin 1. Tay-Sachs Disease
B. Heparan and Dermatan Sulfate 2. Niemann-Pick Disease
C. Glucocerebrosidase 3. Gaucher's Disease
D. Ganglioside 4. Hurler's Syndrome

Back 54

A - 2
B - 4
C - 3
D - 1

Front 55

Gaucher's disease comes in _ varieties. The most severe is variety _ and the least severe is variety _.

Back 55

Gaucher's disease comes in 3 varieties. The most severe is variety 2 and the least severe is variety 1. (3 is intermediate)

Front 56

Type 1 (Classic) Gaucher's disease affects (Infants or Adults?) and (Does or Does Not?) involve the CNS.

Back 56

Type 1 (Classic) Gaucher's disease affects Adults and Does Not involve the CNS.

Front 57

Gaucher's cells:
A) Are located in the bone marrow, liver and spleen
B) Have a fibrillary cytoplasm
C) Appear like crinkled tissue paper
D) Have stacks of lipids in the lysosomes under EM
E) C + D
F) All of the above

Back 57

F

Front 58

What is another name for muchopolysaccharoidosis 1 (MPS 1)?

Back 58

Hurler's Syndrome

Front 59

Which enzyme is deficient in MPS 1 (Hurler's Syndrome)?
A) Sphingomyelinase
B) Hexosaminidase
C) Alpha-L-Iduronidase
D) Glucocerebrosidase
E) Alpha Glucosidase

Back 59

C

(A - Niemann-Pick, B - Tay Sachs, D - Gaucher's, E - Pompe's)

Front 60

Which TWO of the following accumulate in Hurler's syndrome?
A) Cholesterol
B) Heparan Sulfate
C) Chondroitin Sulfate
D) Hyaluronan
E) Dermatan Sulfate

Back 60

B + E

Front 61

Where would you NOT expect to find balloon cells and zebra bodies in MPS 1?
A) Phagocytes
B) Hepatocytes
C) Endothelium
D) Smooth Muscle
E) Neurons
F) Fibroblasts

Back 61

B

Front 62

Which, if any, of these clinical symptoms are NOT typical of Hurler's Syndrome:
A) Hepatosplenomegaly
B) Skeletal Deformities
C) Blindness
D) MI
E) Cardiac valvular deformations and lesions
F) Brain lesions

Back 62

C

Front 63

Which of the following is not a glycogenosis?
A) Von Gierke's Disease
B) MrArdle's Disease
C) Hunter's Disease
D) Pompe's Disease

Back 63

C -
Hunter's Disease is MPS II, a sister to Hurler's Disease

Front 64

Match the form of glycogenosis to the specific disorder:
A) Hepatic Form 1) McArdle's Disease
B) Myopathic Form 2) Pompe's Disease
C) Acid Maltase Def. 3) Von Gierke's Disease

Back 64

A - 3
B - 1
C - 2

Front 65

Match the enzyme to the disorder:
A) Glu-6 Phophatase 1) McArdle's Disease
B) Muscle Phosphorylase 2) Pompe's Disease
C) Acid Maltase/alpha-glucosidase 3) Von Gierke's Disease

Back 65

A - 3
B - 1
C - 2

Front 66

Which glycogenosis is associated with hepatomegaly, hypoglycemia and 50% mortality?

Back 66

Von Gierke's

Front 67

Which glycogen disorder is asssociated with painful cramps with exercise and failure to produce lactate?

Back 67

McArdle's Disease

Front 68

Which glycogenosis is associated with widespread glycogen deposition, cardiomegaly and carediorespiratory failure at age 2?

Back 68

Pompe's Disease (a milder form only leads to skeletal muscle involvement with chronic myopathy).

Front 69

Review of glycogenolysis:
Phosphorylase cuts one glucose off chain (defect in muscle --> McArdle's)
Glu-6 Phosphatase cleaves off last branched glucose (defect --> Von Gierke's)
Acid Maltase normally cleaves maltase, a 2-glucose glycogen (defect --> Pompe's Disease)

Back 69

Quiz: name the enzyme + location of Von Gierke's, McArdle's and Pompe's diseases.

Front 70

Which ONE OR MORE of the following glycogenoses involve lysosomal storage?
A) Von Gierke's disease
B) McArdle's disease
C) Pompe's disease

Back 70

C only

Front 71

What is a tophus?

Back 71

A deposit of uric acid crystals in soft tissue

Front 72

Why is uric acid especially prone to forming crystals in the body?

Back 72

Plasma concentration is just below crystallization point. (around 7mg/dL)

Front 73

Gout affects which ONE OR MORE of the following populations?
A) young males
B) middle-aged males
C) older males
D) premenopausal women
E) postmenopausal women

Back 73

B, C, E

Front 74

What percentage of cases of gout is secondary; that is, due to some other disorder?

Back 74

10%

Front 75

Approximately what percentage of cases of gout is due to an unknown cause?

Back 75

90%; 2/3rds is apparently due to overactive purine production of unknown etiology

Front 76

Gout can be caused by:
A) Overproduction of uric acid
B) Underexcretion of uric acid
C) Both

Back 76

C

Front 77

Lesch-Nyhan Syndome matches all of the following EXCEPT:
A) deficiency in purine recycling
B) mutated HGPRT enzyme
C) self-mutilation
D) primary gout
E) severe neurologic impairment

Back 77

D;
Lesch-Nyhan is a known genetic disorder - thus, it leads to secondary gout.

Front 78

Which of the following cells are lysed by UA crystals in gout?
A) monocytes
B) basophils
C) neutrophils
D) eosinophils

Back 78

C;
They are lysed after phagocytosing the UA crystals, releasing hydrolytic enzymes and cytokines, causing inflammation

Front 79

The following joints are listed in order of most commonly affected by gout to least; which does not belong on the list?
Great toe, instep, ankle, shoulder, knee, wrist

Back 79

shoulder

Front 80

Risk factors for gout include all of the following EXCEPT:
A) Obesity
B) Cigarette Smoking
C) Alcohol
D) High intelligence

Back 80

B

Front 81

Why is the big toe probably most affected by gout?

Back 81

Low temperature, trauma

Front 82

Tophi ARE NOT common in...
A) The olecranon
B) Patella
C) Helix and antihelix of ear
D) Cauda equina
E) Periarticular ligaments

Back 82

D - urate doesn't cross the BBB

The olecranon's part of the elbow... I'd forgotten back and limbs.

Front 83

Kidney involvement in gout includes all of the following EXCEPT:
A) Acute uric acid nephropathy due to intratubular deposits
B) Nephrolithiasis (stones in collecting system)
C) Glomerulonephritis
D) Chronic urate nephropathy

Back 83

C
~20% of patients die from renal failure

Front 84

Describe each of these three stages of gout:
1. Asymptomatic hyperuricemia
2. Acute gouty arthritis
3. Chronic tophaceous gout

Back 84

1. occurs in 25-33% of relatives of gout patients
2. flare-ups of arthritis followed by long remissions
3. persistant disabling joint disease following many acute attacks