Lysosomal Storage Disease

Question 1

What are the disease that can be caused by changes with sphingolipids?

Answer 1

Fabry’s disease (deficiency of alfa-galactosidase A)

Gaucher’s disease (deficiency of glucocerebrosidade)

Niemann Pick disease (deficiency of acid sphingomyelinase)

Krabbe’s disease (deficiency galactocerebrosidase)

Tay-Sachs disease (deficiency of hexosaminidase A)

Metachromatic Leukodystrophy (deficiency of arylsulfatase A)

Question 2

What are the diseases that can be caused by changes in glycosaminoglycans?

Answer 2

Hurler’s syndrome (dificiency of a alfa-L-iduronidase)

Hurter’s syndrome (deficiency of iduronate 2-sulfatase)

Question 3

What is the disease that can be caused by alfa galactosidase A deficiency?

Answer 3

Fabri’s disease

Question 4

What is the disease that can be caused by glucocerebrosidase deficiency?

Answer 4

Gaucher’s disease

Question 5

What is the disease that can be caused by acid sphingomyelinase deficiency?

Answer 5

Niemann-Pick disease

Question 6

What is the disease that can be caused by galactocerebrosidase deficiency?

Answer 6

Krabber’s disease

Question 7

What is the disease that can be caused by hexosaminidase A deficiency?

Answer 7

Tay-Sachs disease

Question 8

What is the disease that can be caused by arylsulfatase A deficiency?

Answer 8

Metachromatic leukodystrophy

Question 9

What is the disease that can be caused by alfa-L-iduronidase deficiency?

Answer 9

Hurler’s syndrome

Question 10

What is the disease that can be caused by iduronate 2-sulfatase deficiency?

Answer 10

Hunter’s syndrome

Question 11

What are the classic symptoms that can be seen in Fabry’s disease?

Answer 11

Child with pain in hands/feet
Lack of sweat
Skin findings

Acummulation of ceramide trihexoside!!!

Question 12

What are the classic symptoms that can be seen in Gaucher’s disease?

Answer 12

Child of Ashkenazi Jewish descent
Splenomegaly on exam
Anemia
Bruising (low plaquets)
Joint pain/fractures

Accumulation of glucocerebroside!!

Question 13

What are the classic symptoms that can be seen in Niemann-Pick disease?

Answer 13

Previously well, healthy child
Weakness, loss of motor skills
Enlarged liver or spleen on physical exam
Cherry red spot

Accumulation of sphingomyelin!!!

Question 14

What are the classic symptoms that can be seen in Krabbe’s disease?

Answer 14

Only neuro symptoms -> progressive weakness, development delay, floppy limbs, loss of head control, absent reflexes, optic atrophy, often fever without infection, usually death < 2 yrs

Globoid cell leukodystrophy

Question 15

What are the classic symptoms that can be seen in Tay-Sachs disease?

Answer 15

3-6 months old infant
Ashkenazi Jewish descendent
Development delay
Exaggerated startle response
Cherry red spot
NO hepatosplenomegaly
Lysosomes with onion skinning

Accumulation of GM2 ganglioside

Question 16

What are the classic symptoms that can be sem in Metachromatic leukodystrophy disease?

Answer 16

~ 2 years old (Krabbe’s disease <6 months)
Ataxia
Hypotonia
Dementia can develop

Accumulation of sulfatides!!

Question 17

What are the classic symptoms that can be sem in Hurler’s disease?

Answer 17

Facial abnormalites (coarse features)
Short stature
Intellectual disability
Hepatosplenomegaly
Dysostosis Multiplex
Corneal clouding
Ear, sinus, pulmonary infections (thick secretions)
Airway obstruction and sleep apneia (tracheal cartilage abnormalities)

Accumulation of heparan and dermatan sulfate

Symptoms 1st year of life.

Question 18

What are the classic symptoms that can be sem in Hunter’s syndrome?

Answer 18

Later onset (1-2 years)
No corneal clouding
Behavioral problems
Learning difficult
Trouble sitting still
Often agressive behavior

Question 19

Explain what is the cause of I Cell Disease?

Answer 19

Subtype of mucolipidosis disorders
Accumulation of both: sphingolipid and mucopolysaccharide

Question 20

What are the symptoms that can be seen in I Cell Disease?

Answer 20

Similiar Hurler’s
Growth failure
Coarse facial features
Hypotonia/motor delay
Clouded corneas
Joint abnormalities
Dysostosis multiple
Frequent respiratory infections

Question 21

What is the importance of mannose-6-phosphate (M6P)?

Answer 21

This is processing in Golgi apparatus. Added to lysosome proteins and directs enzymes to lysosome.

Question 22

What is the disease that can be seen in failure of processing in the Golgi of M6P?

Answer 22

I Cell Disease

Question 23

What are the key findings in I Cell Disease?

Answer 23

Deficient intracellular enzyme levels
Increased extracellular enzyme levels
Multiple enzymes abnormal
Intracellular inclusions in lymphocytes and fibroblasts.

Question 24

What is the problem that can be seen in Pompe’s Disease?

Answer 24

Accumulation of glycogen in lysosomes due acid alpha glucosidase deficiency.