Unit 2 Abali Lecture 7 Glycogen Storage Diseases Flashcards
What is a glycogen storage disease?
When glycogen is not stored properly, macromolecules accumulate in the cells and cause cell death
Glycogen storage diseases and the liver
liver is unable to breakdown glycogen, which leads to hypoglycemia (low blood sugar)
Glycogen storage disease and the muscles
weakness, exercise fatigue, heart failure
What type of disease is glycogen storage diseases?
autosomal recessive
Schiff test
stains glycogen on liver biopsy, which tells us if the person has a glycogen storage disease or not
Name the 7 glycogen storage diseases
von Gierke
Pompe
Cori
McArdle
Hers Disease
Tarui disease
Glucose 6 phosphate dehydrogenase deficiency
Enzyme for von Girke
deficiency of glucose 6 phosphatase
2 types of von girke
T1: Deficiency in glucose 6 phosphatase, Enzyme that Converts glucose 6 phosphate to glucose in the liver
T2: Type 2: deficient in glucose 6 phosphatase translocase, which transfers G6P from cytosol to the ER
Dangers of von girke (explain the chemical mechanism)
Liver cant convert G6P to glucose, so G6 Phosphate builds up in the liver
Very badly impaired gluconeogenesis and glycogenolysis
The muscles are forced to break down glycogen for energy instead
Lactate in the blood is converted to glucose via the Cori cycle in gluconeogenesis, which does not happen since glucose 6 phosphatase is missing. This leads to lactic acidosis
Clinical Aspects of Von Gierke (symptoms)
Shows up in infancy
Poor growth, impaired limbs, doll like face, hepatomegaly (enlarged liver)
Hypoglycemia
Acidosis
Acidosis and hypoglycemia combined can lead to severe intellectual disability
Other symptoms of Von Girke
High cholesterol due to poor liver function → Causes pancreatitis
Kidney enlargement due to glycogen backup
High uric acid → gout → joint pain
Liver cancer due to hepatic adenomas
Treatment von girke
uncooked corn starch throughout day and night
Avoid lactose, fructose and sucrose because they can cause G6 Phosphate to accumulate
Allopurinol: gout
Bicarbonate: acidosis
ACE (angiotensin-converting enzyme): kidney dysfunction
Fibrates: high triglycerides
Von Girke and the Cori cycle
Liver uptake of lactate and its conversion to glucose
Glucose → lactate → glucose
Key to remember: the liver starts producing crazy amounts of lactate!
Lactate produced by the liver CANNOT be converted to glucose
CORI CYCLE DOES NOT WORK!
Pompe disease enzyme
lysosomal alpha 1,4-glucosidase
Pompe disease mechanism
Lysosomal storage disease, glycogen accumulates in lysosomes
Lack of alpha 1,4 glucosidase leads to accumulation of glycogen
Symptoms of pompe
Symptoms in infancy: macroglossia (enlarged tongue), weakness, hypotonia (low muscle tone),
hypertrophic cardiomyopathy
The liver is still enlarged due to fluid build up caused by heart failure
Creatine kinase elevation (shows muscle damage)
Lack of alpha glucosidase via genetic testing
Treatment for pompe disease
Test for elevated levels of creatine kinase
Enzyme replacement therapy and gene therapy is the only hope
Most kids die at 1yrs old due to heart failure
Cori disease enzyme
Deficiency in debranching enzyme: alpha 1,6 glucosidase
Cori disease mechanism
Very similar to von Girke, just milder
Less severe hypoglycemia because gluconeogenesis still works!
Cori cycle still works! So lactate can be converted to glucose!
Debranching enzyme is importance for the muscle, so cori disease can lead to muscle and heart damage 🙁
Treatment - cori
High glucose and high protein
No need to avoid lactose, sucrose or fructose because G6P accumulation is not a concern
McArdle Disease enzyme
MYOPHOSPHORYLASE –>required to continue glycogen break down even after debranching
Clinical aspects and symptoms - McArdle
Report muscle cramps
Dark urine due to break down of myoglobin (muscle break down causes high amounts of myoglobin to show up in the blood)
Surprisingly, they feel fatigued the first 10 minutes of exercise, but then perk up due to vasodilation
(SECOND WIND)
Adolescence or young adulthood
Treatment - McArdle
Enzyme assay and gene analysis
Reproduce second wind by 15 min cycle test
ischemic forearm exercise test: which was developed by Dr McArdle himself.
During this test, a blood pressure cuff is placed on a patient doing forearm exercises (opening and closing the fist) and blood is drawn. In someone with McArdle disease, there would be no increase in lactate.
Patients should carb up and not do strenuous exercise
Hers disease enzyme
Lack of hepatic glycogen phosphorylase
