Genetic diseases II Flashcards Preview

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Flashcards in Genetic diseases II Deck (83):
1

True or false: AR diseases have much more uniform expression than AD

True

2

True or false: AR diseases often have complete penetrance

True

3

When do AR usually present, early, middle, or late in life?

Early

4

AR proteins usually show what mutation?

Loss of function

5

True or false: all inborn errors of metabolism are AR

True

6

Which are more common, AR or AD diseases?

AR

7

True or false: AD diseases usually skip generations

False-AR

8

Alkaptonuria is the result of a deficiency of what enzyme?

Homogentisic acid oxidase

9

What is the pathogenesis of alkaptonuria?

Homogentisic acid binds to cartilage, turning it blue-black

10

Urine that turns black upon standing = ?

alkaptonuria

11

What is the reaction that homogentisic acid oxidase catalyzes?

Homogentisic acid to maleyacetoacetic acid

12

What is the major symptom of alkaptonuria?

Early onset osteoarthritis d/t deposition of homogentisic acid in cartilage

13

What part of the body is susceptible to the osteoarthritis caused by alkaptonuria?

Vertebral discs

14

True or false: cartilage is the only place where homogentisic acid is deposited?

False--tendons as well

15

Black skin spots around the ears = ?

alkaptonuria

16

What is the general problem in lysosomal storage disease?

Lysosomes do not function correctly, thus causing a buildup of materials in a lysosome. This can cause cells death

17

What is the enzyme that is affected in Tay-sachs?

Hexosaminidase A

18

What is the enzyme that is affected in Gaucher's disease?

Glucocerebrosidase

19

What is the enzyme that is affected in Niemann-pick disease?

Sphingomyelinase

20

What is the enzyme that is affected in mucopolysaccharidoses?

Induronidase

21

What is the major accumulating metabolite in Tay sachs?

CM2 ganglioside

22

What is the major accumulating metabolite in Gaucher's disease?

glucocerebroside

23

What is the major accumulating metabolite in Niemann pick disease?

Sphingomyelin

24

What is the major accumulating metabolite in Hurler's and hutner's syndrome?

Dematan sulfate, heparan sulfate

25

What is the enzyme deficiency in Hunter's syndrome? Hurlers?

Hulers = alpha-L-iduronidase
Hunters = L-iduronosulfate sulfatase

26

What is the enzyme that is affected in Gaucher's disease?

-Beta-Glucocerebrosidase

27

What is the therapeutic agent for Pompe's disease?

Myozyme

28

What is the therapeutic agent for Hunter's syndrome?

Elaprase

29

What is the therapeutic agent for Hurler's syndrome?

Aldurazyme

30

Tay-Sach's disease is caused by what mutation in what gene?

Frameshift mutation in the HexA gene

31

What are the symptoms of Tay-sachs? Pathogenesis?

MR and blindness after birth d/t accumulation of ganglioside accumulation

32

When does death occur in pts with Tay-sachs?

before age 4

33

What are the LM histological findings of Tay-sachs?

Swollen neurons

34

Membranous concentric bodies in neurons on EM = ?

Tay-sachs disease

35

Cherry red spot = what disease? Why?

Tay-sachs or Niemann Picks type A d/t increased deposition

36

What is the cherry red spot?

Enhanced macula d/t deposition of material around it. Seen in Tay-sachs and Niemann-Picks type A

37

What is the most common lysosomal storage disease?

Gaucher's disease

38

What is the pathogenesis in Gaucher's disease?

Accumulation of glucocerebrosides (ceramide + glucose) within lysosomes of macrophages

39

On what chromosome is the gene for glucocerebrosidase?

1q

40

What are Gaucher cells?

Macrophages with accumulation of glucoceramide

41

What are the histological findings of Gaucher's disease?

Macrophages with wrinkled tissue paper appearance

42

Which type of Gaucher's is most common (1, 2, or 3)? Which is most severe?

1 = most common
2 = most severe

43

Which type(s) of Gaucher's have neuropathic involvement (1, 2, or 3)?

2 and 3

44

What are the symptoms of type 1 Gaucher's? Pathogenesis?

Asymptomatic to skeletal deformities/hepatosplenomegaly d/t macrophage accumulations

45

What are the symptoms of type 2 Gaucher's?

Type III +
Hydrops fetalis
Progressive neuro degeneration

46

What are the symptoms of type 3 Gaucher's?

Parkinsonian
Eye movement disorders

47

Which type of Gaucher's disease is seen in higher incidence amongst Ashkenazi jews?

Type I

48

What are the symptoms of type 1 Gaucher's? Pathogenesis?

Asymptomatic to skeletal deformities/hepatosplenomegally d/t macrophage accumulations

49

What are the symptoms of type 2 Gaucher's? Pathogenesis?

Type III +
Hydrops fetalis
Progressive neuro degeneration

50

What are the symptoms of type 3 Gaucher's? Pathogenesis?

Parkinsonian
Eye movement disorders

51

What is the treatment for Gaucher's disease?

Imiglucerase (cerezyme)

52

What is the mutation of type A and B Niemann-Pick's disease? What is the gene affected?

Missense mutation in acid sphingomyelinase

53

What is the mutation of type C Niemann-Pick's disease? What is the gene affected?

Deficiency in cholesterol transport--NOT an enzyme defect

54

What are the symptoms of type A Niemann-Picks disease?

Neurological defects

55

What are the symptoms of type B Niemann-Picks disease?

Hepatosplenomegaly

No CNS involvement

56

What is the mutation of type A and B Niemann-Pick's disease?

Missense mutation in acid sphingomyelinase

57

What are the symptoms of type B Niemann-Picks disease?

Hepatosplenomegaly

No CNS involvement

58

In what cells does sphingomyelin accumulate in Niemann-Picks disease?

Macrophages

59

Zebra body macrophages = what disease?

Niemann-Picks

60

What is the mutation in type C Niemann-Picks disease? What does this cause? What is deposited in macrophages?

NPC1--defect in choleserol transport, causing increased deposition of GM1 and GM2

61

Which is most common Type A, B or C of Niemann-Picks disease?

Type C

62

What are the symptoms of type C Niemann-Picks disease?

Progressive neurological damage (ataxia, dystonia etc)

63

What is NP1 protein in Niemann picks type C?

G-coupled protein receptor to get cholesterol out of the lysosome

64

What is NP2 protein in Niemann picks type C?

Transporter of cholesterol

65

As pts with Niemann-Picks disease age, what happens to their neurological symptoms? Systemic symptoms?

Systemic go down
Neuro go up

66

What are the four major diseases that have an increased incidence in the Ashkenazi Jewish population?

1. CF
2. Gaucher's disease
3. Niemann-Pick
4. Taysachs

67

What is the general problem with mucopolysaccharidoses?

Defect in lysosomal enzymes that degrade mucopolysaccharides, causing a buildup in lysosomes of muscle tissues

68

Which has a milder course: Hurler's or Hunter's syndrome?

Hunter

69

What are the histological characteristics of MPS?

cleared cytoplasm in cells

70

What is the inheritance pattern for Hunters syndrome? Hurlers?

Hunters = XLR
Hurler's = AR

71

What are the symptoms of Hurler's syndrome? (2)

Gargoyle children with EITHER progressive MR OR aortic valve problems

subendothelial arterial deposits in the coronary arteries

72

What are the symptoms of Hunter's syndrome? (2)

mild hepatosplenomegaly

subendothelial arterial deposits in the coronary arteries

73

What symptom is common to Hurler's and Hunter's syndrome?

subendothelial arterial deposits in the coronary arteries

74

Which has corneal clouding: Hurler's or Hunter's syndrome?

Hurler's

75

True or false: there is an enzyme replacement therapy for both Hurler's and Hunter's syndrome

True

76

What is the enzyme deficiency in von Gierke's disease, (type I), and what does this cause (3)?

Glucose-6-phosphatase

Hepatomegaly, hypoglycemia, hyperlipidemia,

77

What is the enzyme deficiency in Pompe's disease, (type III), and what does this cause (3)?

Acid maltase

Floppy baby, Cardiomegally, cardiorespiratory failure

78

What are the names of Type I, III, and V GSDs?

I = Von Gierke's disease
V= McArdle's disease
III = Pompe's disease

79

What is the enzyme deficiency in McArdle's disease, (type V), and what does this cause (2)?

Muscle phosphorylase

Painful cramps with exercise +myoglobin uria

80

Floppy baby + glossomegaly + cardiomegaly = ?

Pompe's disease (type III GSD)

81

What is the stain used to highlight carbs?

PAS

82

Hepatomegaly + Xanthomas + gout + hypoglycemia + hyperlipidemia + convulsion = what disease?

Type I GSD (von Gierke's)

83

True or false: McArdle's syndome have normal muscle strength

True