Nutrition care in Children having Metabolic disease named "GSD"

1. Glycogen Storage
Diseases(GSD)
Dr. Atta ur Rehman
28th May, 2014
Prince Muhammad Bin Abdulaziz Hospital, AlMadinah

3. Enteral Nutritional Therapy :
Emerging new paradigms ?
Yanbu, Kingdom of Saudi Arabia
April 29-30, 2014

4. Enteral Nutritional Therapy :
Emerging new paradigms ?
Yanbu, Kingdom of Saudi Arabia
April 29-30, 2014

5. Why Glycogen Storage ?
• Glycogen is a readily mobilized storage
form of glucose
• ¾ of total body glycogen in the muscles
• Liver glycogen 90gm (5% of the liver)
• Muscle glycogen 245gm(0.7% of muscles)
• Extra cellular glycogen 10gm(0.1%)

6. Why Glycogen Storage ?
• Glycogen is a sugar used as a fuel for
energy especially in the brain and in
muscles.
• Unlike fatty acids, the released glucose can
provide energy in the absence of oxygen
and can thus supply energy for anaerobic
activity.

7. Overview of Glycogen Metabolism
• Excess glucose stored as glycogen
• Glucose units joined by α-1,4 and α -1,6 glycosidic
bonds
• Glucosyl chains are branched
• Fasted state (catabolic)—glycogen breakdown
• Fed state (anabolic)—glycogen synthesis

8. Anabolism – Glycogenesis
• Glycogen synthase needs to be activated for glycogenesis
to occur
• Enzymes involved in breakdown need to be deactivated
• Fed state dominated by insulin
• Protein phosphatase I activated (also inactivates
phosphorylase kinase, not shown below)

9. Catabolism - Glycogenolysis
• Fasted state dominated by glucagon and epinephrine
• Signalling cascade results in activation of glycogen
breakdown and turns off glycogenesis (mutually
antagonistic)
– Through activation of protein kinase A, enzymes
become phosphorylated
• Phosphoglucose mutase converts G1P  G6P
• Glucose-6-phosphatase to remove Pi from
G6Pglucose (in the liver)

10. Treatment of several inborn
errors of metabolism
• Glycogen storage disease (GSD, also glycogenosis and
dextrinosis) is the result of defects in the processing of
glycogen synthesis or breakdown within muscles, liver, and
other cell types.[1] GSD has two classes of cause:

11. Glycogen Storage disease
• Glycogen storage disease (GSD, also
glycogenosis and dextrinosis) is the
result of defects in the processing of
glycogen synthesis or breakdown within
muscles, liver, and other cell types.[1] GSD
has two classes of cause:

12. Glycogen Storage disease
GSD has two classes of cause:
• Genetic: Genetic GSD is caused by any inborn
error of metabolism (genetically defective
enzymes) involved in these processes.
• Acquired: In livestock, acquired GSD is caused by
intoxication with the alkaloid castanospermine.[2]

13. Treatment of several inborn
errors of metabolism
• Glycogen storage disease (GSD, also glycogenosis and
dextrinosis) is the result of defects in the processing of
glycogen synthesis or breakdown within muscles, liver, and
other cell types.[1] GSD has two classes of cause:

14. Treatment of several inborn
errors of metabolism
• Glycogen storage disease (GSD, also glycogenosis and
dextrinosis) is the result of defects in the processing of
glycogen synthesis or breakdown within muscles, liver, and
other cell types.[1] GSD has two classes of cause:

15. GSD Type 1
• Edgar von Gierke’s Disease
• Most common disease type (approximately 1 in 20,000
infants)
•Characterized by:
-an abnormally large abdomen
due to an accumulation of
glycogen in the liver
-prominent hypoglycemia in
between meals (may cause
convulsions in infants)

16. Deficiency of the Enzyme
glucose-6-phosphatase
•An inherited defect in chromosome 17
•The body is not able to break down glycogen into glucose
Glucagon
Cascade

17. Mutation in the
glucose-6-phosphate transporter
Lumen of Endoplasmic Reticulum

18. Prolonged hypoglycemia can cause
Glucagon production
Accumulation of
glucose-6-phosphate
 Glycolysis
pyruvate and
lactate
Fat Breakdown
Beta-oxidation
Excess acetyl CoA
 Ketones

19. Treatment of several inborn
errors of metabolism
• Glycogen storage disease (GSD, also
glycogenosis and dextrinosis) is the result of
defects in the processing of glycogen synthesis or
breakdown within muscles, liver, and other cell
types.[1] GSD has two classes of cause:

20. Treatment of several inborn
errors of metabolism
• Glycogen storage disease (GSD, also
glycogenosis and dextrinosis) is the result of
defects in the processing of glycogen synthesis or
breakdown within muscles, liver, and other cell
types.[1] GSD has two classes of cause:

21. Treatment of several inborn
errors of metabolism
• Glycogen storage disease (GSD, also
glycogenosis and dextrinosis) is the result of
defects in the processing of glycogen synthesis or
breakdown within muscles, liver, and other cell
types.[1] GSD has two classes of cause:

22. Treatment of several inborn
errors of metabolism
• Glycogen storage disease (GSD, also
glycogenosis and dextrinosis) is the result of
defects in the processing of glycogen synthesis or
breakdown within muscles, liver, and other cell
types.[1] GSD has two classes of cause:

23. Treatment of several inborn
errors of metabolism
• Glycogen storage disease (GSD, also
glycogenosis and dextrinosis) is the result of
defects in the processing of glycogen synthesis or
breakdown within muscles, liver, and other cell
types.[1] GSD has two classes of cause:

24. Treatment of several inborn
errors of metabolism
• Glycogen storage disease (GSD, also
glycogenosis and dextrinosis) is the result of
defects in the processing of glycogen synthesis or
breakdown within muscles, liver, and other cell
types.[1] GSD has two classes of cause:

25. Treatment of several inborn
errors of metabolism
• Glycogen storage disease (GSD, also
glycogenosis and dextrinosis) is the result of
defects in the processing of glycogen synthesis or
breakdown within muscles, liver, and other cell
types.[1] GSD has two classes of cause:

26. Treatment of several inborn
errors of metabolism
• Glycogen storage disease (GSD, also
glycogenosis and dextrinosis) is the result of
defects in the processing of glycogen synthesis or
breakdown within muscles, liver, and other cell
types.[1] GSD has two classes of cause:

27. Treatment of several inborn
errors of metabolism
• Glycogen storage disease (GSD, also
glycogenosis and dextrinosis) is the result of
defects in the processing of glycogen synthesis or
breakdown within muscles, liver, and other cell
types.[1] GSD has two classes of cause:

28. Nutrition Strategy-GSD
GSD I, glucose-6-phosphate cannot be
dephosphorylated to free glucose. Managing this
condition entails overnight continuous gastric high-
carbohydrate feedings; frequent daytime feedings
with energy distributed as 65% carbohydrate, 10% to
15% protein, and 25% fat; and supplements of
uncooked cornstarch.
J Am Diet Assoc. 1993 Dec;93(12):1423-30.

29. Nutrition Strategy-GSD
In GSD III, gluconeogenesis is enhanced to help maintain endogenous
glucose production.
In contrast to treatment for GSD I, advocated treatment for GSD III
comprises frequent high-protein feedings during the day and a high-
protein snack at night; energy is distributed as 45% carbohydrate, 25%
protein, and 30% fat.
J Am Diet Assoc. 1993 Dec;93(12):1423-30.

30. Nutrition Strategy-GSD
Patients with GSD IV, VI, and IX have
benefited from high-protein diets similar to
that recommended for patients with GSD III.
J Am Diet Assoc. 1993 Dec;93(12):1423-30.

31. Nutrition Strategy-GSD
Study shows that patients with McArdle (GSD V) disease can
improve their maximal work capacity and exercise tolerance to
submaximal workloads by maintaining a diet high in
carbohydrate instead of protein.
The carbohydrate diet not only improves tolerance to everyday
activities, but will probably also help to prevent exercise-induced
episodes of muscle injury in McArdle disease.
J Neurol Neurosurg Psychiatry. 2008 Dec;79(12):1359-63.

32. Nutrition Strategy-GSD
• Short- to long-term overnight intermittent
administration of uncooked cornstarch
prevents nocturnal hypoglycaemia in GSD-
1a children more effectively than
continuous nocturnal feeding of dextrose.
• J Hum Nutr Diet. 2013 Aug;26(4):329-39

33. Nutrition Strategy-GSD
The basis of dietary therapy is nutritional
manipulation to prevent hypoglycemia and improve
metabolic dysfunction, with the use of continuous
nocturnal intragastric feeding or cornstarch therapy at
night and foods rich in starches with low
concentrations of galactose and fructose during the
day and to prevent hypoglycemia during the night.
J Pediatr Gastroenterol Nutr. 2008 Aug;47 Suppl 1:S15-21

34. Nutrition Strategy-GSD
• Short- to long-term overnight intermittent
administration of uncooked cornstarch
prevents nocturnal hypoglycaemia in GSD-
1a children more effectively than
continuous nocturnal feeding of dextrose.
• J Hum Nutr Diet. 2013 Aug;26(4):329-39

35. Nutrition Strategy-GSD
• Short- to long-term overnight intermittent
administration of uncooked cornstarch
prevents nocturnal hypoglycaemia in GSD-
1a children more effectively than
continuous nocturnal feeding of dextrose.
• J Hum Nutr Diet. 2013 Aug;26(4):329-39

36. Treatment of several inborn
errors of metabolism

37. Summary
• Nutrition Therapy Goals in GSD according to the
type of disease:
a) Restriction (global or partial) of one or more nutritional
components become "toxic" because of the occurring enzymatic
defect;
b) Supplement with defective nutritional component;
c) Eliminate the accumulated "toxic" compounds via Diet

38. Summary
It is still unclear whether long-
term complications can all be
prevented by dietary therapy.
However, with earlier diagnosis,
appropriate diet, and better
metabolic control, many
individuals with GSD are doing
very well and many adults are
living longer and healthier lives.

39. References
• Arenas, J., Martin, M., Andreu, A. (2006) Glycogen Storage Disease Type V. USA: University of Washington.
• Association for Glycogen Storage Disease. (2001). Typeviigsd. Retrieved from http://www.agsdus.org/html/typeviigsd.html
• Association for Glycogen Storage Disease. (2008). Typeiigsd. Retrieved from http://www.agsdus.org/html/typeiigsd.html
• Association for Glycogen Storage Disease. (2009). Typevigsd. Retrieved from http://www.agsdus.org/html/typevigsd.html
• Association for Glycogen Storage Disease. (2006). Type0gsd. Retrieved from http://www.agsdus.org/html/type0gsd.html
• Berg, J.M., Tymoczko, J.L., Stryer, L. (2012) Biochemistry. New York: W. H. and Freeman Company.
• Dagli, A., Sentner, C., Weinstein, D. (2010) Glycogen Storage Disease type III. USA: University of Washington.
• Dagli, A. I., & Weinstein, D. A. (2011). Glycogen Storage Disease Type VI. Retrieved from
http://www.ncbi.nlm.nih.gov/books/NBK5941/
• Genetics Home Reference. (2013) Glycogen Storage Disease type III. Retrieved from http://ghr.nlm.nih.gov/condition/glycogen-
storage-disease-typ e-iii
• Genetics Home Reference. (2013) Glycogen Storage Disease type IV . Retrieved from http://ghr.nlm.nih.gov/condition/glycogen-
storage-disease-type-iv
• Genetics Home Reference. (2013) Glycogen Storage Disease type V. Retrieved from http://ghr.nlm.nih.gov/condition/glycogen-
storage-disease-type-v
• Genetics Home Reference. (2010). Glycogen storage disease type VI. Retrieved from http://ghr.nlm.nih.gov/condition/glycogen-
storage-disease-type-vi
• Genetics Home Reference. (2010). Pompe disease. Retrieved from http://ghr.nlm.nih.gov/condition/pompe-disease
• Hendriksz, C., & Gissen, P. (2010). Glycogen storage disease. Paediatrics and Child Health, 21(2), 84-89.
• Leslie, N., & Tinkle, B. T. (2013). Glycogen Storage Disease Type II (Pompe Disease). Retrieved from
http://www.ncbi.nlm.nih.gov/books/NBK1261/