Glycogen Storage Disease Type 1 (GSD I) or Von Gierke's Disease is a liver disease. The disease is caused by increased glucose accumulation in the liver. The disease results in various complications as described in the article. The significant effects of glucose accumulation is swelling of the liver as well as the kidneys.1 In this article, we will discuss in detail the different causes, symptoms, and treatment of Glycogen Storage Disease Type 1 (GSD I) or Von Gierke's Disease.
How Is Glycogen Storage Disease Type 1 (GSD I) or Von Gierke's Disease Defined?
- Glucose to Glycogen Storage1-
- The carbohydrate is digested in stomach and intestine to form glucose.
- Glucose is absorbed and used for energy production as well as to provide energy for muscle contraction.
- Surplus of glucose is stored in liver as glycogen.
- Glycogen to Glucose1-
- In between the breakfast, lunch and dinner glycogen is converted to glucose.
- The disease is caused by insufficient or absence of enzyme, which converts glycogen to glucose.
- The lack of enzyme, which converts glycogen to glucose, causes serious disease known as In Glycogen Storage Disease of Type-I/ von Gierke's disease.
- Glycogen Storage Disease1, 2
- The disease is caused by increased storage of glycogen and decreased breakage of glycogen to glucose.
- Glycogen Storage Disease Type I, also known as Von Gierke's disease.
- Von Gierke's disease is the commonest form of Glycogen Storage Disease, which is 25% of all cases of Glycogen Storage Disease.
- Congenital Disease-
- Glycogen Storage Disease/ Von Gierke's disease is an inherited medical condition, which primarily affects energy metabolism i.e., the method by which the body converts food into energy.
- Disease is caused by genetic abnormalities.
- Blood glucose level remains low 1 to 2 hours after intake of food.
- Patient develops symptoms and signs of hypoglycemia.
- Hypoglycemia Causes Following Symptoms-
- Chronic hunger
- Extreme fatigue
- Irritable behavior
- Symptoms are observed in infants.
- Liver Failure-
- Glucose is stored in liver and kidney as glycogen.
- The cells of liver and kidney are unable to convert glycogen to glucose.
- Slow accumulation of glycogen in liver and kidney causes liver and kidney enlargement.
- Despite this, the liver performs its functions quite normally and usually there is no noted liver failure.
Causes of Glycogen Storage Disease Type 1 (GSD I) or Von Gierke's Disease
- Genetic Disorder-
- Glycogen Storage Disease Type 1 (GSD I) or Von Gierke's Disease as stated is an inherited medical condition.
- Autosomal recessive genetic disorder results in lack of enzyme glucose-6-phosphatas.
- Enzyme Glucose-6-Phosphatase Deficiency1-
- The enzyme influences liver cell to breakdown glycogen to glucose to maintain constant normal blood sugar level.
- Enzyme helps to maintain normal sugar level even during fasting hour in normal individuals.
a. Enzyme Translocase Abnormality-
- Enzyme gucose-6phosphatase is transported by enzyme translocase.
- Abnormality of enzyme translocase causes low concentration or absence of enzyme glucose-6-phosphatase.
Symptoms of Glycogen Storage Disease Type 1 (GSD I) or Von Gierke's Disease
Symptoms Caused By Hypoglycemia-
a. Symptoms During Mild To Moderate Hypoglycemia-
- Extreme hunger
b. Symptoms During Moderate Hypoglycemia-
- Clammy Extremities
c. Symptoms During Severe Hypoglycemia-
d. Delayed Symptoms Caused By Hypoglycemia-
- Failure to grow
Abnormal Abdominal Clinical Signs:
- Enlarged liver with normal liver enzyme and bilirubin
- Abdominal swelling
Symptoms Caused By Lactic Acidosis-
- Severe metabolic acidosis is caused by hypoglycemia and breakdown of fatty acids. Symptoms of Acidosis Are As Follows-
- Rapid breathing
- Dehydration- Causes increased heart rate and low blood pressure
- Symptoms of Hyperuricemia
- Joint pain
- Uric acid level is elevated in blood
- Uric acid nephropathy
Symptoms Caused By Kidney Failure-
- Glycogen Deposit
- Enlarge kidney by 20%
- Uric Acid Nephropathy
Symptoms Caused By Abnormal Blood Clotting-
- Excessive Bleeding-
- Epistaxis- nasal bleeding
- Bleeding following brushing teeth
Diagnosis of Glycogen Storage Disease Type 1 (GSD I) or Von Gierke's Disease
Symptoms are obvious before child is one year old. Investigations are done as soon as symptoms are observed.
- Hypoglycemia- Low blood sugar
- Lactic Acidosis2- Blood lactic acid level is elevated.
- Hypertriglyceridemia- Blood triglyceride level is elevated.
- Hyperuricemia2- Blood uric acid level is increased (6 to 12 mg/dl).
- Hepatomegaly- enlarged liver.
- Splenomegaly- enlarged spleen.
CT Scan and MRI (Magnetic Resonance Imaging)
- Hepatomegaly- enlarged liver.
- Splenomegaly- enlarged spleen.
- Glycogen storage abnormalities observed.
- Electron microscopy study of liver biopsy3
Treatment For Glycogen Storage Disease Type 1 (GSD I) or Von Gierke's Disease
The Treatment of Glycogen Storage Disease Type 1 (GSD I) or Von Gierke's Disease is aimed at early diagnosis and medical management. Medical management has improved life expectancy.4
- Early diagnosis
- Treat lactic acidosis
- Treat hyperuricemia
- Treat hypoglycemia
- Treat infection-
- Viral infection- antiviral medications
- Bacterial infection- antibiotic medications.
- Diet Change Treatment is very beneficial as corn starch gets digested very slowly because of which there is a steady release of glucose between feeding.
- Uncooked cornstarch mixed in water
- Soy formula
- Soy milk
- Frequent meals during day
- Overnight tube feeding
Liver and Kidney Transplant Surgery5-
- Used as research protocol
- Research suggest may prevent Hepatoma.5
1. Glucose-6-phosphatase deficiency.
Froissart R1, Piraud M, Boudjemline AM, Vianey-Saban C, Petit F, Hubert-Buron A, Eberschweiler PT, Gajdos V, Labrune P.
Orphanet J Rare Dis. 2011 May 20;6:27.
2. Glycogen storage disease type Ia: linkage of glucose, glycogen, lactic acid, triglyceride, and uric acid metabolism.
Sever S1, Weinstein DA, Wolfsdorf JI, Gedik R, Schaefer EJ.
J Clin Lipidol. 2012 Nov-Dec;6(6):596-600.
3. Electron microscopy: a method for the diagnosis of inherited metabolic storage diseases. Electron microscopy in diagnosis.
Pathol Res Pract. 1980 May;167(1):118-35.
4. Consensus guidelines for management of glycogen storage disease type 1b - European Study on Glycogen Storage Disease Type 1.
Visser G1, Rake JP, Labrune P, Leonard JV, Moses S, Ullrich K, Wendel U, Smit GP; European Study on Glycogen Storage Disease Type I.
Eur J Pediatr. 2002 Oct;161 Suppl 1:S120-3.
5. Preemptive liver-kidney transplantation in von Gierke disease: a case report.
Marega A1, Fregonese C, Tulissi P, Vallone C, Gropuzzo M, Toniutto PL, Baccarani U, Bresadola F, Toso F, Montanaro D.
Transplant Proc. 2011 May;43(4):1196-7. doi: 10.1016/j.transproceed.2011.03.003.
6. Prevention of hepatocellular adenoma and correction of metabolic abnormalities in murine glycogen storage disease type Ia by gene therapy.
Lee YM1, Jun HS, Pan CJ, Lin SR, Wilson LH, Mansfield BC, Chou JY.
Hepatology. 2012 Nov;56(5):1719-29.