Q: About GSD and Glycogen structure (C-09)


 

Andersen’s Disease is a rare disease caused by the deficit of the Branching enzyme, responsible for the formation of branches in glycogen structure. This results in an abnormal glycogen with few branching points and long peripheral chains. Clinically, hepatoesplenomegaly, cirrhosis of the liver and hepatic failure are major concerns. As the problem is located in the branching points, it is obvious that there is a defect in the formation of:

 

a)     Alpha 1,4 -O-glycosidic linkages

 

b)     Alpha 1,6 -O-glycosidic linkages

 

c)      Alpha 1 ,Beta 2 -O-glycosidic linkages

 

d)     Beta1,3 -O-glycosidic linkages

 

e)     Beta1,4 -O-glycosidic linkages

 

f)       Beta1,6 -O-glycosidic linkages

 

Q: About the finding of an abnormal glycogen


 

Question about Carbohydrate Metabolism (CM-12)

Glycogen structure

Glycogen structure

 

A liver biopsy is done on a child with hepatomegaly and mild fasting hypoglycemia. Hepatocytes show accumulation of glycogen granules with single glucose residues remaining at the branch points near the periphery of the granule. The most likely genetic defects is in the activity of:

 

a)     Alpha 1,6, glycosidase

 

b)     Alpha 1,4-alpha 1,4 glucan transferase

 

c)      Glucokinase

 

d)     Glucose 6 phosphatase

 

e)     Glucuronyl transferase

 

f)       Glycogen synthase

 

g)     Phosphoglucomutase

 

h)    UDP-glucose-Uridyl transferase

 

 

A: About Glycogen Storage Diseases


Answer to CM-01: ( c) 

 The deficit of debranching enzyme produces the Glycogen Storage Disease Type III, AKA Cori Disease. It is an autosomal recessive disorder characterized by abnormal molecules of glycogen with short branches. The lack of activity of this enzyme in the liver results in hypoglycemia, since the patient can not use the hepatic glycogen to release glucose to blood during the intermeal periods. The lack of the enzyme in the muscles contributes to the patient weakness and fatigue. Accumulation of glycogen in hepatocytes and muscle, including the cardiac muscle, damage the structures and interfere with their function (Note the increased activity of specific enzymes, hepatomegaly and ventricular hypertrophy in this patient). The diagnosis is confirmed when a deficit of debranching enzyme is found in liver or muscle tissue. Fibroblasts and lymphocytes may also show the deficiency.   

 Deficit of (a), (b) and (e) would not produce an accumulation of glycogen since these enzymes participates in the synthesis. (d) is not related to metabolism of Glycogen, but with metabolism of bilirrubin.  If there was a Deficit of  (f) glucose 6 phosphatase (Glycogen Storage Disease Type I) the response to glucagon would be very impaired and the hypoglycemia would be very sever,  since the conversion of glucose 6 phosphate to glucose catalyzed by this enzyme, is key not only in the use of liver glycogen, but also in gluconeogenesis, so the patient would depend only in the diet glucose for his metabolic requirements. 

 

 

 

Additional information:

 

 

A very good review about Glycogen Storage Diseases can be found at:

Tegay, D: Glycogen-Storage Disease Type III

 

…and this is an interesting video that I found in youtube about the Histopathology of Heart and Liver in Glycogen storage Disease

 

 

 

 For those visitors interested in Histology and Histopathology, I suggest to review the videos of WashingtonDeceit’s channel in youtube:

http://www.youtube.com/user/WashingtonDeceit.

They are great!