What is Glycogen? What is its role in our body?

Glycogen is the storage form of glucose (sugar) in the body. It is a complex material made of individual glucose molecules linked together in long chains with many branches off the chains (just like a tree). Glycogen is mainly stored in the liver and muscle cells, but the kidneys and intestines also store some limited amounts of glycogen.

 

Metabolism is the process by which our body breaks down the food we eat and converts it to energy. 

A simple form of sugar, called glucose, is our bodies’ main source of energy. After we eat, we have too much glucose in our blood, so our bodies store the extra glucose in the form of glycogen (much like we deposit our extra money in a bank). When our bodies need more energy, certain enzymes convert the glycogen back to glucose and withdraw it from the liver and the muscles (just like we withdraw spending money from the bank).

 

What are Glycogen Storage Diseases (GSDs)?

GSDs are inherited genetic metabolic diseases. The underlying problem in all the GSDs is the use and storage of glycogen.

 

A person who has a metabolic disorder has a difficult time breaking down certain foods and creating energy. Metabolic disease is most frequently caused by an absence or deficiency in an enzyme

(or protein). An enzyme can act to help the body break down food into energy.

A person with a GSD has an absence or deficiency of one of the enzymes responsible for making or breaking down glycogen in the body.  The enzyme deficiency causes either abnormal tissue concentrations of glycogen (too much or too little) or incorrectly or abnormally formed glycogen

(Shaped wrong).

 

What are symptoms of GSD?

Depending upon the deficient enzyme each GSD has different clinical features. Some GSDs also have heterogeneous symptoms. GSDs can affect the liver only, the muscles only, or both the liver and the muscles. Other systems that may be involved include blood cells (red blood cells, white blood cells, and platelets), heart, and kidneys amongst others.

 

What are types of GSDs and their symptoms?

The main types of GSDs are categorized by number and name and those affecting the liver include:

 

• Type I  Von Gierke disease, defect in glucose-6-phosphatase)-most common type of GSD; accounts for 90% of all GSD cases
• Type III            Cori’s disease, debrancher enzyme deficiency)
• Type IV            Andersen’s disease, brancher enzyme deficiency)
• Type VI            Hers’ disease, liver phosphorylase deficiency)
• Type IX            Liver glycogen phosphorylase kinase)  
• Type 0              Glycogen synthase deficiency
• Type XI            Fanconi Bickel Syndrome

 

 

What are the most common presentations of GSDs?

Type 0

• Early age at presentation
• Fasting low blood sugar (irritability, crying until fed, waking up in the night and demanding food)
• Increased lactate levels in the blood
• Fasting ketone bodies in the blood

Type I

• Low blood sugar with few hours of fasting
• Impaired growth and delayed puberty
• Increased mouth ulcers and infections
• Large and fatty liver and kidneys
• High levels of lactate, fats, and uric acid in the blood
• Osteoporosis (weak bones with increase risk of fractures)

  Type III

• Swollen abdomen due to an enlarged liver
• Growth delay during childhood
• Low blood sugar after prolong fasting
• Elevated fat levels in blood
• Possible muscle weakness

Type IV

• Growth delay in childhood
• Enlarged liver
• Progressive cirrhosis of the liver (which may lead to liver failure)
• May affect muscles and heart in late-onset type

Type VI, IX

• Low blood sugar
• Liver enlargement occurs, but diminishes with age

Type XI

• Rickets (soft bones which may be distorted typically resulting in bow legs)
• Renal tubular acidosis
• Liver and kidney failure

How are GSDs Diagnosed?

 

• Specific symptoms (as described above), age at onset of symptoms, laboratory parameters help in diagnosing GSDs.
• Furthermore, Liver biopsy helps to show excess accumulation of Glycogen within liver cells (hepatocytes) with special stains and certain tests.
• Enzyme assay in the liver tissue – to diagnose specific enzyme deficiency, but this test is not easily available
• Genetic mutation analysis.

 

How are GSDs treated?

Goals in treatment of GSDs are:

Prevent low blood sugars

Correct metabolic derangements

Support optimal growth and development

The goal of treatment is to maintain normal blood glucose levels. This may be done with:

 

 

 

Frequent high carbohydrate meals during the day.

 

For some children, eating several small meals rich in sugars and starches every day helps prevent blood sugar levels from dropping.

 

Cornstarch. For some young children, giving uncooked cornstarch every four to six hours – including during overnight hours – also can help keep blood sugar levels from getting low. Corn starch acts as slow release form of glucose. However one must avoid cooked cornstarch as it leads to sudden rise in blood sugar level followed by rapid fall.

 

Medium chain triglycerides (coconut oil, pure ghee, butter) in type I

 

High protein diet in type III GSD

 

Continuous night-time feeding. In order to maintain the blood glucose level, a special feeding tube can be placed into the child’s stomach.  The feeding tube is then used to give formula with a high concentration of glucose. This helps control the blood sugar level

 

Eliminate foods that are high in fructose or lactose – in type 1 GSD

 

Medications:

Allopurinol—reduces uric acid levels in the blood to prevent gout and kidney stones.

Lipid lowering agents to decrease high cholesterol, LDL in body.

 

Is liver transplantation an option for GSDs?

Liver transplant can potentially cure the child of the disease and treat complications.

Overall GSDs do not do well with transplant as are multisystem problems. Type I GSDs are usually transplanted when the adenomas become malignant.  Type I may need liver + kidney transplant (if kidney failure has set in)

 

What are the potential complications of GSDs?

 

When the disease is untreated or inadequately treated for long duration following complications can occur

 

• Gout (arthritis of typically the smaller bones of feet, acute joint pain)
• High lipid levels
• Pancreatitis
• Type II Diabetes mellitus
• Hepatic adenomas -----in Type I in 20’s or 30’s
• Hepatocellular Carcinoma (liver cancer)
• Liver cirrhosis ----Type IV, maybe III and IX
• Renal disease ---hypertension, stones, renal dysfunction
• Recurrent infections – Type I b
• Liver, kidney, heart failure

 

 

 

 

What is the life expectancy of a person with glycogen storage disease?
 

The life expectancy of persons with type I, III, and VI is probably somewhat reduced although many do quite well. The patients with type IV die in early childhood.

 

 

 

Can glycogen storage disorders be prevented?

 

Most of the glycogen storage disorders are hereditary conditions (most of them Autosomal recessive) that run in families. If someone else in your family, or if you personally, or one of your existing children, has a glycogen storage disorder, your doctor may refer you to a geneticist (a gene specialist). The geneticist will be able to discuss the likelihood of your future child, or children, having a glycogen storage disorder.

When a woman becomes pregnant, there is also the possibility of having some tests carried out early in the pregnancy, to determine if the unborn baby has a glycogen storage disorder. The tests involve taking a sample of amniotic fluid from around the baby. This allows the doctor to study the levels of the enzymes in the amniotic fluid and therefore determine whether the unborn baby has a glycogen storage disorder.

 

 

 

 

References 
 

Neutrophilia and elevated serum cytokines are implicated in glycogen storage disease type Ia
So Youn Kim, Li-Yuan Chen, Wai Han Yiu, David A. Weinstein, Janice Y. Chou
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Glucose-6-phosphatase deficiency
Roseline Froissart, Monique Piraud, Alix Mollet Boudjemline, Christine Vianey-Saban, François Petit, Aurélie Hubert-Buron, Pascale Trioche Eberschweiler, Vincent Gajdos, Philippe Labrune
Orphanet J Rare Dis. 2011; 6: 27. 

Prevention of Hepatocellular Adenoma and Correction of Metabolic Abnormalities in Murine Glycogen Storage Disease Type Ia by Gene Therapy

Young Mok Lee, Hyun Sik Jun, Chi-Jiunn Pan, Su Ru Lin, Lane H. Wilson, Brian C. Mansfield, Janice Y. Chou
Hepatology. Author manuscript; available in PMC 2013 November 1.

Gene Therapy for Type I Glycogen Storage Diseases
Janice Y. Chou, Brian C. Mansfield
Curr Gene Ther. Author manuscript; available in PMC 2008 September 26.
FEBS Lett. Author manuscript; available in PMC 2008 September 26.

The glycogen storage diseases
Brenda E. Ryman
J Clin Pathol Suppl (R Coll Pathol) 1974; 8: 106–121. FEBS Lett. 

Liver transplantation for glycogen storage disease types I, III, and IV
D. Matern, T. E. Starzl, W. Arnaout, J. Barnard, J. S. Bynon, A. Dhawan, J. Emond, E. B. Haagsma, G. Hug, A. Lachaux, G.P.A. Smit, Y-T. Chen
Eur J Pediatr. Author manuscript; available in PMC 2010 December 21.

Use of modified cornstarch therapy to extend fasting in glycogen storage disease Types Ia and Ib,
Catherine E Correia, Kaustuv Bhattacharya, Philip J Lee, Jonathan J Shuster, Douglas W Theriaque, Meena N Shankar, G Peter A Smit, David A Weinstein
Am J Clin Nutr. Author manuscript; available in PMC 2013 October 25.

 

Glycogen storage disease types I and II: Treatment updates
D. D. Koeberl, P. S. Kishnani, Y. T. Chen
J Inherit Metab Dis. Author manuscript; available in PMC 2009 June 8.

Liver transplantation for glycogen storage disease Types I, III, and IV
D. Matern, T. E. Starzl, W. Arnaout, J. Barnard, J. S. Bynon, A. Dhawan, J. Emond, E. B. Haagsma, G. Hug, A. Lachaux, G.P.A. Smit, Y-T. Chen
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Updated 16th June 2014