Lysosomal diseases FA 111

Question 1

deficiency in Hexosaminidase A

Answer 1

Tay Sacs Disease

Question 2

Accumulation of GM2 gangliosidase

Answer 2

Tay Sacs Disease

Question 3

Accumulation of Ceramide trihexoside

Answer 3

Fabry Disease

Question 4

Deficiency of alpha- galactosidase A

Answer 4

Fabry Disease

Question 5

Accumulation of sulfatides – in particular Cerebroside sulfate

Answer 5

Metachromatic Leukodystrophy

Question 6

Deficiency in Arylsufatase

Answer 6

Metachromatic leukodystrophy

Question 7

Deficiency in Galactocerebrosidase

Answer 7

Krabbe Disease

Question 8

Accumulation of Galactocerebroside

Answer 8

Krabbe Disease

Question 9

Accumulation of Glucocerebroside

Answer 9

Gaucher Disease

Question 10

Deficiency of Glucocerbrosidase or beta glucosidease

Answer 10

Gaucher Disease

Question 11

Accumulation of sphingomyelin

Answer 11

Niemann-Pick Disease

Question 12

Deficiency in sphingomyelinase

Answer 12

Niemann- Pick Disease

Question 13

Deficiency in alpha-L- iduronidase

Answer 13

Hurler Syndrome

Question 14

Deficiency in Iduronate Sulfatase

Answer 14

Hunter Syndrome

Question 15

Accumulation of Heparan Sulfate + Dermatan sulfate

Answer 15

Hunter/ Hurler syndrome

Question 16

Metachromatic Leukodystrophy

Deficiency

Accumulation

Symptoms

Answer 16

Deficiency: Arylsulfatase A
Accumulation of Cerebral sulfate

• Central and peripheral demyelination with ataxia and dementia
• impaired production and destruction of myelin sheath

Question 17

Krabbe Disease

Deficiency

Accumulation

Symptoms

Answer 17

Galactocerebrosidase

Galactocerebroside

Peripheral neuropathy
Developmental delay
Optic atrophy
Globoid cells
Fever in abscess of infection
Irritability
 death by 2 years of age usually

Question 18

Niemman Pick disease

Deficiency

Accumulation

Symptoms

Answer 18

Sphingomyelinase

Sphingomyelin

Progressive neuropathy
Hepatosplenomegally
Foam cells (lipid ladened macrophages)
“Cherry red” spot on the macula

Question 19

Gaucher disease

Deficiency

Accumulation

Symptoms

Tx

Answer 19

most common

Glucocerebrosidase

Glucocerebroside

Hepatosplenomegally
Aseptic necrosis of femur
Bone crisis: pancytopenia, osteoporosis
Gaucher cells – resembled crumpled piece of paper

Tx: recombinant clucocerebrosidase

Question 20

Who has cells that look like crumpled pieces of paper

Answer 20

Gaucher cells — Gaucher disease

Question 21

If you see a cherry red spot on the macula, how are you going to differentiate between the two possible causes?

Answer 21

Niemann pick vs tay sacs

If hepatosplenomegaly is seen then it is Niemann pick’s disease.

Question 22

Tay Sacs Disease

Deficiency

Accumulation

Symptoms

Answer 22

Hexosaminidase A

GM2 ganglioside

Progressive neuropathy
Cherry red spot on the macula
Lysosomes with onion skin
No hepatosplenomegaly

Question 23

if you see lysosomes that look as if they have “onion” skin

Answer 23

Tay Sacs diesease

Question 24

Fabry Disease

Deficiency

Accumulation

Symptoms

Answer 24

X-Linked Recessive

Alpha-galactosidase A

Ceramide trihexoside

Peripheral neuropathy of hands and feet
Angiokeratomas
Cardiovascular disease
Renal Disease

Question 25

Hurler syndrome Deficiency Accumulation Symptoms

Answer 25

alpha-L- iduronidase heparan sulfate and dermatan sulfate ``` Gargoylism Developmental delay (dwarfism) airway obstruction CORNEAL CLOUDING hepatosplenomegaly ```

Question 26

Hunter Syndrome Deficiency Accumulation Symptoms

Answer 26

Iduronate Sulfate Heparan Sulfate and Dermatan sulfate mild hurler + aggressive behavior NO CORNEAL CLOUDING

Question 27

If on analysis you see an increase in heparan sulfate and dreamt sulfate, what are the two options you have and how are you going to differentiate between them?

Answer 27

Hurler syndrome or Hunter Syndrome - is there corneal clouding? - and enzyme deficiency