Lysosomal Storage Diseases

Question 1

Lysosomal storage disease is caused by / results in

Answer 1

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

Question 2

Lysosomal storage diseases - types and diseases

Answer 2

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

Question 3

Sphingolipidoses mode of inheritance

MC?

Answer 3

AR except FABRY disease (XR)

MC: Gaucher disease

Question 4

Fabry disease pathophysiology and mode of inheritance

Answer 4

a-galactosidase A deficiency

XR. The only sphingolipidoses that is not AR

Question 4

a-galactosidase A action

Answer 4

Ceramide trihexoside to glucocerebroside

Question 5

Fabry disease - presentation

Answer 5

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

Question 6

Fabry disease accumulation

Answer 6

Ceramide trihexoside

Question 7

Niemann-pick disease pathophysiology

Answer 7

Sphingomyelinase deficiency

Question 8

Sphyngomyelinase action

Answer 8

Sphyngomyelin to ceramide

Question 9

Niemann-Pick /accumulation of

Answer 9

Sphingomyelin

Question 10

Most common sphingolipidosis

Answer 10

Gaucher disease

Question 11

Niemman-pick disease findings

Answer 11

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

Question 12

Gaucher disease pathophysiology

Answer 12

Glucocerebrosidase (β-glucosidase)

Question 13

Gaucher disease accumulation

Answer 13

Glucocerebroside

Question 15

Gaucher findings

Answer 15

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

Question 15

Gaucher disease treatment

Answer 15

Recombinant glucocerebrosidase

Question 16

Gaucher cells

Answer 16

Lipid-laden macrophages resembling crumpled tissue paper

Question 17

Tay-Sachs disease pathophysiology

Answer 17

Hexosaminidase A deficiency

Question 18

Bone crisis?

Answer 18

Severe bone pain

Question 19

Hexosaminidase A action

Answer 19

GM2 ganglioside to GM3

Question 20

Tay-Sachs disease accumulation

Answer 20

GM2 ganglioside

Question 21

Tay-Sachs disease findings

Answer 21

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

Question 22

Niemann-PIck vs Tay-Sachs disease

Answer 22

Niemman pick has hepatosplenomegaly

Question 23

Krabbe disease pathophysiology

Answer 23

Galactocerebrosidase deficiency

Question 24

Galactocerebrosidase action

Answer 24

Galactocerebroside to ceramide

Question 25

Krabbe disease accumulation

Answer 25

Galactocerebroside, psychosine

Question 26

Krabbe disease findings

Answer 26

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

Question 27

Metachromatic leukodystrophy pathophysiology

Answer 27

Arylsulfatase A

Question 28

Arysulfatase A action

Answer 28

Sulfatides to galactocerebroside

Question 29

Metachromatic leukodystrophy accumulation

Answer 29

Cerebroside sulfate

Question 30

Metachromatic leukodystrophy findings

Answer 30

Central and peripheral demyelination with ataxia and dementia

Question 31

Sphingolipidoses with globoid cells

Answer 31

Krabbe disease

Question 32

Sphingolipidoses with lysosome with onino skin

Answer 32

Tay-Sachs disease

Question 33

Sphingolipidoses with cherry red spot on macule

Answer 33

Niemman pick disease | Tay sachs disease

Question 34

Mucopolussaccharidoses accumulation

Answer 34

Heparan sulfate | Dermatan sulfate

Question 35

Name 2 mucopolusaccharidoses and mode of inheritance

Answer 35

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

Question 36

Hurler syndrome pathophysiology

Answer 36

a-L-iduronidase

Question 38

Hunter syndrome pathophysiology

Answer 38

Iduronate sulfatase deficiency

Question 39

Hurler syndrome symptoms

Answer 39

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

Question 39

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

Answer 39

Ashkenazi Jews

Question 40

Sphingolipidose with hepatosplenomegaly

Answer 40

Niemann-Pick disease | Gaucher disease

Question 41

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

Answer 41

Ashkenazi Jews

Question 42

Sphingolipidose with aseptic femur necrosis

Answer 42

Gaucher

Question 43

Sphingolipidose with optic atrophy

Answer 43

Krabbe disease

Question 44

Sphingolipidose with angiokeratomas

Answer 44

Fabry

Question 46

Sphingolipidose with developmental delay

Answer 46

Krabbe disease | Tay-Sachs disease

Question 47

Metachromatic leukodystrophy enzyme deficiency

Answer 47

Arysulfatase A

Question 48

Sphingolipidose - Ashkenazi Jews

Answer 48

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

Question 49

Hunter syndrome - symptoms

Answer 49

Mild Hurler + aggressive behavior, no corneal clouding