glycogen storage diseases

Question 1

von geirke cause

Answer 1

glucose - 6- phosphatase deficiency (liver)
releases free glucose from G6P

Question 2

two types of von gierke:

Answer 2

type 1a - glucose-6-phosphatase deficient
type 1b - glucose-6-phosphate transorter 1 deficient

Question 3

consequences of von gierke:

Answer 3

primary defect - high G6P (middle man!) - high downstream

-hypoglycemia (ramp up glycolysis)
-hyperlipidemia (pyruvate to acetyl CoA)
-hyperalaninemia
-hyperuricemia
-lactic acidemia (high pyruvate)

Question 4

clinical features of von gierke:

Answer 4

neonatal period 3-4 months presentation
severe - patients die
infants have doll-like appearance due to excess adipose (hyperlipidemia)
glycogen accumulation - kidney and liver enlargement

Question 5

treatment for von gierke:

Answer 5

nocturnal infusion of glucose
glycolysis is ramped up and glucose is being burned through - hypoglycemia

treatment to try to keep sugars up

Question 6

cause of pompe disease:

Answer 6

acid maltase (alpha-glucosidase) deficiency
AKA lysosomal hydrolase

normally, alpha-glucosidase hydrolyzes alpha 1,4 and 1,6 glycosidic linkages at an acidic pH and hydrolyzes glycogen

causes glycogen accumulation

Question 7

what is pompe disease?

Answer 7

accumulation of glycogen within vacuoles of all tissues
most notably, cardiac and muscle

Question 8

symptoms of pompe disease:

Answer 8

early onset - classical infantile

cardiomegaly, hepatomegaly
hypotonia (floppy baby syndrome)
muscle weakness
trouble breathing
death before 1 yo

Question 9

symptoms of late onset pompe disease:

Answer 9

20s-60s

affects mostly musculoskeletal muscles
“myopathic”

Question 10

pompe treatment:

Answer 10

myozyme-alglucosidase alpha enzyme replacement therapy (ERT)

Question 11

cori/forbes disease mutation:

Answer 11

glycogen debranching enzyme (alpha 1,6 glucosidase) deficient

Question 12

what is cori/forbes disease?

Answer 12

accumulation of abnormally structured glycogen having shorter outer chains

Question 13

symptoms of cori/forbes disease:

Answer 13

can’t mobilize glycogen? decreased glucose.

hepatomegaly
ketotic hypoglycemia
hyperlipidemia
variable skeletal myopathy
cardiomyopathy
poor growth

Question 14

treatment for cori/forbes:

Answer 14

same sx as von gierke - therefore, want to increase glucose levels.

high carbohydrate meals with corn starch supplement
high protein diet - promote gluconeogenesis
no effective treatment for the cardiomyopathy

Question 15

anderson disease cause:

Answer 15

autosomal recessive
glycogen branching enzyme deficient
accumulation of abnormal glycogen that has poor solubility in liver (few branch points)
looks like amylopectin (plants)

Question 16

sx of anderson disease:

Answer 16

progressive hepatomegaly

Question 17

classic anderson disease:

Answer 17

first few months of life
progressive hepatomegaly
failure to thrive - liver failure
liver transplant to survive

Question 18

anderson disease progression:

Answer 18

liver cirrhosis
portal vein hypertension
esophageal varices and ascites
death by 5 yo

Question 19

anderson disease variant:

Answer 19

multi system (skeletal, cardiac, nerve, liver)
mostly affects peripheral nerves

Question 20

McArdle disease mutation:

Answer 20

glycogen phosphorylase deficient

Question 21

McArdle disease charcateristics:

Answer 21

can’t mobilize glucose
exercise intolerance
muscle cramps
attacks of rhabdomyolysis with myoglobinuria (burgundy color urine)
increases in serum CK
increased serum lactic acid and ammonia (protein metabolism) upon exercise

Question 22

Hers disease mutation:

Answer 22

liver glycogen phosphorylase deficient
breaks glycogen into G1P
decreased glucose

Question 23

results of Hers disease:

Answer 23

hypoglycemia
may use fats for energy - ketosis
glycogen accumulates in liver cells - enlarged and dysfunctional