glycogen storage diseases Flashcards
von geirke cause
glucose - 6- phosphatase deficiency (liver)
releases free glucose from G6P
two types of von gierke:
type 1a - glucose-6-phosphatase deficient
type 1b - glucose-6-phosphate transorter 1 deficient
consequences of von gierke:
primary defect - high G6P (middle man!) - high downstream
-hypoglycemia (ramp up glycolysis)
-hyperlipidemia (pyruvate to acetyl CoA)
-hyperalaninemia
-hyperuricemia
-lactic acidemia (high pyruvate)
clinical features of von gierke:
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
treatment for von gierke:
nocturnal infusion of glucose
glycolysis is ramped up and glucose is being burned through - hypoglycemia
treatment to try to keep sugars up
cause of pompe disease:
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
what is pompe disease?
accumulation of glycogen within vacuoles of all tissues
most notably, cardiac and muscle
symptoms of pompe disease:
early onset - classical infantile
cardiomegaly, hepatomegaly
hypotonia (floppy baby syndrome)
muscle weakness
trouble breathing
death before 1 yo
symptoms of late onset pompe disease:
20s-60s
affects mostly musculoskeletal muscles
“myopathic”
pompe treatment:
myozyme-alglucosidase alpha enzyme replacement therapy (ERT)
cori/forbes disease mutation:
glycogen debranching enzyme (alpha 1,6 glucosidase) deficient
what is cori/forbes disease?
accumulation of abnormally structured glycogen having shorter outer chains
symptoms of cori/forbes disease:
can’t mobilize glycogen? decreased glucose.
hepatomegaly
ketotic hypoglycemia
hyperlipidemia
variable skeletal myopathy
cardiomyopathy
poor growth
treatment for cori/forbes:
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
anderson disease cause:
autosomal recessive
glycogen branching enzyme deficient
accumulation of abnormal glycogen that has poor solubility in liver (few branch points)
looks like amylopectin (plants)
sx of anderson disease:
progressive hepatomegaly
classic anderson disease:
first few months of life
progressive hepatomegaly
failure to thrive - liver failure
liver transplant to survive
anderson disease progression:
liver cirrhosis
portal vein hypertension
esophageal varices and ascites
death by 5 yo
anderson disease variant:
multi system (skeletal, cardiac, nerve, liver)
mostly affects peripheral nerves
McArdle disease mutation:
glycogen phosphorylase deficient
McArdle disease charcateristics:
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
Hers disease mutation:
liver glycogen phosphorylase deficient
breaks glycogen into G1P
decreased glucose
results of Hers disease:
hypoglycemia
may use fats for energy - ketosis
glycogen accumulates in liver cells - enlarged and dysfunctional
