DMH-B Test 3 Week 5- Glycogen Storage Diseases

What is the final step in releasing glucose from glycogen?

A1,6 linkage is removed by a glucosidase enzyme that releases glucose directly.

What is andersen disease? Compare to GSD type 0.

Andersen disease (GSD IV) is an autosomal recessive disease that presents early in childhood. It affects glycogen synthesis, but unlike GSD type 0 there is abnormal glycogen structure and hypoglycemia is uncommon in the early stages. (caused by deficiency branching enzyme)

What are the 4 different types of GSD III?

IIIa: Affects liver and muscle IIIb: affects just liver IIIc: defect in glucosidase activity IIId: transferase activity.

What causes the nephrolithiasis in von Gierke's disease?

DUe to a lack of G-6-Pase there is a inability to convert lactate or alanine to glucose, thus causing lactic acidosis, thus lowering the solubility and excretion of uric acid by the kidney.

What tests might allow us to think GSD III vs I?

Elevated serum CK and fibroblast debrancher activity.

What happens to glucose-6-phosphate in the liver and kidney during glycogenolysis?

GLucose-6-phosphate is transported to the endoplasmic reticulum for dephosphorylation then back out into the cytoplasm. Pi stays in the cell while glucose is exported into the blood.

What are the treatments of glycogen storage disease 0?

GSD 0: caused by defect in glycogen synthase. Avoid fasting, give infants frequent protein rich meals avoiding high carb intake. Once pancreatic amylase is being made, give corn starch at night as it takes a long time for pancreatic amylase to break it down thus supplying glucose throughout the night.

What is the main difference between GSD I and III?

GSDIII usually involves the muscles! THus there is hypotonia and muscle wasting. Hypoglycemias are less severe since there is partial removal of glucose from glycogen. So pretty much presents like GSD I, but less severe form.

What causes the hepatomegaly in von Gierke's disease?

Glucose-6-phosphatase is insuffecient, thus G-6-P can't become glucose, instead it increases UA and counteracts the activation of glycogenolysis by glucagon following food deprivation.

COmpare Hers disease and McArdles.

Hers: GSD type VI: lack of glycogen phosphorylase in the LIVER. Presents in childhood. hypoglycemia, hyperlipidemia, and ketosis with hepatomegaly and growth retardation Mcardle: GSD type V: lack of glycogen phosphorylase in the Muscles!!! Much more common. presents teens to 20s: severe exercise intolerance.

Why does hyperlipiedemia occur in von gierke's disease?

Hyperlipidemia occurs because lactate, alanine, and carbons make pyruvate that is converted to acetyl CoA which is a precuror for synthesis of fatty acids and cholesterol leading to the formation and secretion of VLDLs.

What are the signs and symptoms of Pompe's disease?

Hypotonia, weakness, areflexia, cardiomegaly, and hepatomegaly. Usually limited to skeletal muscle weakness.

What is type 0 Glycogen storage disease?

It is an autosomal recessive disease caused by defect in glycogen synthase.

Where is Glucose-6-Phosphatase found?

It is only found in places that produce glucose AKA Liver and Kidney!

WHat is the difference in products of liver glycogenolysis and muscle glycogenolysis?

Liver: Can make glucose Muscle: Can make pyruvate for use in anaerobic glycolysis or Pyruvate to acetyl CoA.

How does glucose-6-Phosphate form in glycogenolysis?

Phosphoglucomutase forms glucose-6-phosphate after it forms from G1P.

What is Pompe's disease?

Pompe's disease AKA Type II glycogen storage disease (GSD) is an autosomal recessive disorder characterized by lysosomal acid maltase (alpha-glucosidase) deficiency in LYSOSOMAL GLYCOGEN.

What causes GSD type III?

THis is caused by a defective debranching enzyme. This is autosomal recessive and known as Cori Disease or Forbes disease

What is the main symptom of andersen disease and why does this happen?

The main symptom of andersen disease is liver failure, hepatomegaly, and failure to thrive. The reason why this occurs is because there is a deficiency in branching enzyme, thus glycogen structure is similar to plant amylose. These long unbranch polymers of glycogen store lots and lots of water (like a potato) causing excessive storage of water in the glycogen held in the liver. Early hypoglycemia doesn't occur, late hypoglycemia does.

What is the role of debranching enzyme and transferase in glycogenolysis?

These 2 enzymes move the final 4 residues of a branch to the end of a chain so that they can be removed by glycogen phosphorylase forming a gluce-1-phosphate

What disease should we think if we hear fasting hypoglycemia with either lactic acidemia, hyperlipidemia, or hepatomegaly?

Think GSD I. It also doesn't present with post prandial hyperglycemia (GSD 0)

What is the importance of branching in glycogen?

This excludes water to decrease tissue osmotic effect and increase efficiency as a substrate for glycogen phosphorylase (glcogenolysis)

What is von Gierke disease? What mutation is it linked to and in what population?

This is GSD Type I where there is a reduced activity of glucose-6-phosphatase in the ER (type Ia) or deficiency of the transporter of G6P (Type Ib). Link with mutation R83C. Seen most commonly with non-ashkenazi Jews.

What are signs and symptoms of von gierke's disease?

This is due to GLucose-6-phosphatase or G6P transporter deficiency Leading to hepatomegaly, adenomas, hypoglycemia, elevated uric acid, hyperlipidemia, nephrolithiasis

What are the signs and symptoms of type 0 Glycogen storage disease and relate this to the pathogenesis of the disease.

Type 0 glycogen storage is caused by a defect in glycogen synthase. Because of this, patients are unable to store excess glucose as glycogen and are unable to pull from glycogen stores when they need it. Thus patients present with morning fatigue and hypoglycemia that responds to feeding. fasting hypoalanemia and blood lactate/ketosis. (unclear MOA of ketosis. Possible lipolysis occurs to use energy creating ketones normally insulin is released to prevent this, but since there is no glucose, insulin secretion is suppressed, thus no insulin to supress lipolysis and ketone formation) Hypoalanemia and blood lactate are low because both are used in gluconeogenesis (since we can't use glucose from glycogen stores) post prandial hyperglycemia, lactic acidemia. Long term effects: short stature (because GH released at night during sleep, but only with adequte glucose release) osteopenia, and neurological damage due to the neuron's dependency in using only glucose as a fuel.

What is the second-wind effect in McArdle's disease?

Type 5 GSD: Can't use glycogen stores in muscles due to glycogen phosphorylase deficiency. As such, fatty acids are used in anaerobic glycolysis, this however, takes time.

How do you diagnose GSD type IV?

culture fibroblasts to test for branching enzymes.

What is the rate limiting step of glycogenesis? what activates it (2 ways)? How does this activation relate to the biochemical process of activation?

glycogen synthase is the RLS. First way It is activated by insulin or lack of epinephrine Therefore glycogen synthase is activated by insulin via (dephosphorylation) since that's what insulin does in storage. Second way it is activated is via GLucose-6-Phosphate which allosterically activates any PHOSPHORYLATED glycogen

What causes hyperalaninemina in type I GSD?

inability to convert lactate or alanine to glucose causes lactic acidemia and hyperalanemia.