Lysosomal Storage Diseases Flashcards Preview

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Flashcards in Lysosomal Storage Diseases Deck (49)
1

Lysosomal storage disease is caused by / results in

Deficiency of one of the many lysosomal enzymes --> accumulation of abnormal metabolic products

2

Lysosomal storage diseases - types and diseases

A. spingolipidoses: 1. Fabry 2. Gaucher 3. Niemann-Pick 4. Tay-Sachs 5. Krabbe 6. Metachromatic leukodystrophy
B. Mucopolysacccharidosrs: 1. Hurler syndrome
2. Hunter syndrome

3

Sphingolipidoses mode of inheritance
MC?

AR except FABRY disease (XR)
MC: Gaucher disease

4

Fabry disease pathophysiology and mode of inheritance

a-galactosidase A deficiency
XR. The only sphingolipidoses that is not AR

4

a-galactosidase A action

Ceramide trihexoside to glucocerebroside

5

Fabry disease - presentation

early: Triad of episodic peripheral neuropathy, angiokeratomas, hypohidrosis
late: progressive renal failure, cardiovascular disease

6

Fabry disease accumulation

Ceramide trihexoside

7

Niemann-pick disease pathophysiology

Sphingomyelinase deficiency

8

Sphyngomyelinase action

Sphyngomyelin to ceramide

9

Niemann-Pick /accumulation of

Sphingomyelin

10

Most common sphingolipidosis

Gaucher disease

11

Niemman-pick disease findings

1. Progressive neurodegeneration
2. Cheery red spot on macule
3. Foam cells (lipid-laden macrophages)
4. Hepatosplenomegaly

12

Gaucher disease pathophysiology

Glucocerebrosidase (β-glucosidase)

13

Gaucher disease accumulation

Glucocerebroside

15

Gaucher findings

1. Hepatosplenomegaly
2. Pancytopenia
3. Aseptic necrosis of femur
4. Gaucher cell
5. Bone crisis
7. osteoporosis

15

Gaucher disease treatment

Recombinant glucocerebrosidase

16

Gaucher cells

Lipid-laden macrophages resembling crumpled tissue paper

17

Tay-Sachs disease pathophysiology

Hexosaminidase A deficiency

18

Bone crisis?

Severe bone pain

19

Hexosaminidase A action

GM2 ganglioside to GM3

20

Tay-Sachs disease accumulation

GM2 ganglioside

21

Tay-Sachs disease findings

1. Progressive degeneration
2. Developmental delay
3. Cherry red spot on macule
4. Lysosomes with onion skin
NO HEPATOSPLENOMEGALY (vs Niemann-Pick)

22

Niemann-PIck vs Tay-Sachs disease

Niemman pick has hepatosplenomegaly

23

Krabbe disease pathophysiology

Galactocerebrosidase deficiency

24

Galactocerebrosidase action

Galactocerebroside to ceramide

25

Krabbe disease accumulation

Galactocerebroside, psychosine

26

Krabbe disease findings

1. Peripheral neuropathy
2. Developmental delay
3. Optic atrophy
4. Globoid cells

27

Metachromatic leukodystrophy pathophysiology

Arylsulfatase A

28

Arysulfatase A action

Sulfatides to galactocerebroside

29

Metachromatic leukodystrophy accumulation

Cerebroside sulfate

30

Metachromatic leukodystrophy findings

Central and peripheral demyelination with ataxia and dementia

31

Sphingolipidoses with globoid cells

Krabbe disease

32

Sphingolipidoses with lysosome with onino skin

Tay-Sachs disease

33

Sphingolipidoses with cherry red spot on macule

Niemman pick disease
Tay sachs disease

34

Mucopolussaccharidoses accumulation

Heparan sulfate
Dermatan sulfate

35

Name 2 mucopolusaccharidoses and mode of inheritance

1. Harler syndrome (AR)
2. Hunter syndrome (XR)

36

Hurler syndrome pathophysiology

a-L-iduronidase

38

Hunter syndrome pathophysiology

Iduronate sulfatase deficiency

39

Hurler syndrome symptoms

1. Developmental delay
2. Gargoylism (abnormal facial features)
3. Airway obstruction
4. Corneal clouding
5. Hepatosplenomegaly

39

Increased incidence of Tay-sachs, Niemann-Pick, some forms of Gaucher disease

Ashkenazi Jews

40

Sphingolipidose with hepatosplenomegaly

Niemann-Pick disease
Gaucher disease

41

Increased incidence of Tay-sachs, Niemann-Pick, some forms of Gaucher disease

Ashkenazi Jews

42

Sphingolipidose with aseptic femur necrosis

Gaucher

43

Sphingolipidose with optic atrophy

Krabbe disease

44

Sphingolipidose with angiokeratomas

Fabry

46

Sphingolipidose with developmental delay

Krabbe disease
Tay-Sachs disease

47

Metachromatic leukodystrophy enzyme deficiency

Arysulfatase A

48

Sphingolipidose - Ashkenazi Jews

increased incidence of Tay-sachs, Niemann-Pick, some forms of Gaucher disease

49

Hunter syndrome - symptoms

Mild Hurler + aggressive behavior, no corneal clouding