Storage Diseases (Glycogen and Lysosomal)

Question 1

Enzyme deficient in Von Gierke’s disease (type I)

Answer 1

• glucose-6-phosphatase

Question 2

Symptoms of Von Gierke’s disease (type I)

Answer 2

• autosomal recessive

- severe fasting hypoglycemia, increased glycogen in liver, increased blood lactate, hepatomegaly

Question 3

Enzyme deficient in Pompe’s disease (type II)

Answer 3

• lysosomal alpha-1,4-glucosidase (acid maltase)

Question 4

Presentation of Pompe’s disease (type II)

Answer 4

• autosomal recessive

- cardiomegaly and systemic findings leading to early death (Pompe’s trashes the pump (heart, liver and muscle))

Question 5

Enzyme deficient in Cori’s disease (type III)

Answer 5

• debranching enzyme (alpha-1,6-glucosidase)

Question 6

Presentation of Cori’s disease (type III)

Answer 6

• autosomal recessive

- milder form of Von Gierke’s with normal blood lactate levels

Question 7

Enzyme deficient in McArdle’s disease (type V)

Answer 7

• skeletal muscle glycogen phosphorylase

Question 8

Presentation of McArdle’s disease (type V)

Answer 8

• autosomal recessive
• increased glycogen in muscle but cannot break it down leading to painful muscle cramps, myoglobinuria with strenuous exercise

Question 9

Enzyme deficiency, accumulated substrate and mode of inheritance of Fabry’s disease

Answer 9

• deficient: alpha-galactosidase A
• substrate: ceramide trihexoside
• inheritance: XR

Question 10

Presentation of Fabry’s disease

Answer 10

• peripheral neuropathy of hands/feet
• angiokeratomas
• cardiovascular/renal disease

Question 11

Enzyme deficiency, accumulated substrate and mode of inheritance of Gaucher’s disease

Answer 11

• deficient: glucocerebrosidase
• substrate: glucocerebroside
• inheritance: AR

Question 12

Presentation of Gaucher’s disease

Answer 12

• hepatosplenomegaly
• aseptic necrosis of femur
• bone crises
• presence of Gaucher’s cells (macrophages that look like crumpled tissue paper)

Question 13

Enzyme deficiency, accumulated substrate and mode of inheritance of Niemann-Pick

Answer 13

• deficient: sphingomyelinase
• substrate: sphingomyelin
• inheritance: AR

Question 14

Presentation of Niemann-Pick

Answer 14

• progressive neurodegeneration
• hepatosplenomegaly
• cherry-red macula
• presence of foam cells (histiocytes)

Question 15

Enzyme deficiency, accumulated substrate and mode of inheritance of Tay-Sachs

Answer 15

• deficient: hexosaminidase
• substrate: GM2 ganglioside
• inheritance: AR

Question 16

Presentation of Tay-Sachs

Answer 16

• progressive neurodegeneration
• developmental delay
• cherry red macula
• lysosomes with onion skin appearance
• NO hepatosplenomegaly (vs. Niemann-Pick)

Question 17

Enzyme deficiency, accumulated substrate and mode of inheritance of Krabbe’s disease

Answer 17

• deficient: galactocerebrosidase
• substrate: galactocerebroside
• inheritance: AR

Question 18

Presentation of Krabbe’s disease

Answer 18

• peripheral neuropathy
• developmental delay
• optic atrophy
• globoid cells

Question 19

Enzyme deficiency, accumulated substrate and mode of inheritance of metachromatic leukodystrophy

Answer 19

• deficient: arylsulfatase A
• substrate: cerebroside sulfate
• inheritance: AR

Question 20

Presentation of metachromatic leukodystrophy

Answer 20

• central and peripheral demyelination with ataxia and dementia

Question 21

Enzyme deficiency, accumulated substrate and mode of inheritance of Hurler’s syndrome

Answer 21

• deficient: alpha-L-iduronidase
• substrate: heparan sulfate, dermatan sulfate
• inheritance: AR

Question 22

Presentation of Hurler’s syndrome

Answer 22

• developmental delay
• gargoylism
• airway obstruction
• corneal clouding
• hepatosplenomegaly

Question 23

Enzyme deficiency, accumulated substrate and mode of inheritance of Hunter’s syndrome

Answer 23

• deficient: iduronate sulfatase
• substrate: heparan sulfate, dermatan sulfate
• inheritance: XR

Question 24

Presentation of Hunter’s syndrome

Answer 24

• mild Hurler’s with aggressive behavior

- NO corneal clouding