Von Gierke Disease - Causes, Symptoms, Diagnosis and Treatment

Introduction:

Von Gierke disease is described as a genetic disorder with a lack of enzymes involved in the glycogen metabolism pathway. Von Gierke first noticed this disease in 1929. Glucose provides the body's energy, stored in the liver and muscles as glycogen. Whenever the body needs glucose like during fasting or increased energy requirement, glycogen from the liver is broken down to release glucose and is supplied to other cells. Due to impairment in the glucose supply to the body, there is a disturbance in maintaining stable and balanced glucose levels in the blood.

What Is Von Gierke Disease?

It is also called glycogen storage disease type 1, an inherited disorder caused by an enzyme deficiency needed to break down glycogen stored in the liver and muscles into glucose. This lack of glycogen metabolism results in low glucose levels in the blood, and excess glycogen and fat accumulate in the liver and kidneys. It is the most common glycogen storage disease among the eight types.

What Are the Types of Glycogen Storage Disease Type 1?

There are two types of glycogen storage diseases, glycogen storage disease 1a (GSD1a), in which there is a deficiency of the enzyme glucose 6-phosphatase(G6Pase), and glycogen storage disease 1b, in which there is a deficiency of the enzyme glucose six phosphate translocase.

How Is Von Gierke Disease Caused?

Since it is a genetic disorder, the main reason is gene mutation. So, there is a mutation of gene G6PC on chromosome 17q21 in the subtype glycogen storage disease type 1a. There is a mutation in the SLC37A4 gene located on chromosome 11q23.3 with an autosomal recessive inheritance pattern. There is a 25 percent chance of acquiring the disease with every pregnancy.

What Are the Signs and Symptoms of Von Gierke Disease?

• The symptoms start appearing in infancy and can also begin during early childhood.

• Hypoglycemia or low blood sugar levels is due to the failure to break down glycogen into glucose.

• Lactic acidosis and ketosis.

• Muscle weakness.

• Failure of general and sexual growth.

• Enlargement of the liver.

• Enlargement of the kidneys.

• Thinning of bone.

• The frequent occurrence of mouth ulcers.

• Recurrent infections.

• Swelling of the belly.

• Low heat tolerance.

• Tendency to bruise very easily.

• Bleeding disorder.

• Tiredness.

• Hunger.

• Irritability.

How Is Von Gierke Disease Diagnosed?

Blood Tests: Laboratory blood tests will present with the following:

• Low sugar levels

  • High lactic acid.

  • High uric acid.

  • High levels of cholesterol.

  • High levels of triglycerides.

• A mild decrease in white blood cells (neutrophils) is called neutropenia, and a severe decrease in white blood cells is called agranulocytosis.

• Genetic Testing: The sequencing of gene molecules in G6PC and SLC37A4 is done to confirm the presence of gene mutations.

• Liver Biopsy: A sample of liver tissue is taken for microscopic examination. The histologic changes in the cells are used to confirm the diagnosis.

What Is the Treatment of Von Gierke Disease?

The primary concern in the treatment involves the management of metabolic disturbances of the blood, attaining normal mental and physical growth, preventing complications, and leading a life of better quality. The major prevention focus is managing hypoglycemia or low blood sugar levels. A few lifestyle and dietary changes are made to prevent the development of hypoglycemia. There should be regular checking of blood sugar levels as there is an increase in the child’s growth and metabolic needs.

• A diet with a surplus amount of complex carbohydrates like whole grains, vegetables, peas, and beans should be consumed.

• Patients with this type of glycogen storage disease should avoid fasting, which will worsen hypoglycemia.

• Since there is a lack of enzymes to convert galactose and fructose, a diet rich in these sugars should be avoided. Sugary drinks, baked foods, fruits, honey, and sweets should be avoided.

• Babies are initially given non-sugar soy-based formula every two to three hours. When the baby sleeps for more than three to four hours, hypoglycemia in sleep can develop. To avoid that, a nasogastric tube or G-tube is inserted through surgery, and parents are given instructions to feed the baby at regular intervals when there is a refusal to eat or when the child is ill. There should also be monitoring of blood sugar levels. There is an increased tendency for infections at the site of tube insertion. So patients are administered a granulocyte colony-stimulating factor before insertion of the tube. Patients on the granulocyte colony-stimulating factor should be evaluated for monthly blood count and spleen size measurements.

• An alternative, cornstarch, which can provide glucose for longer durations and release glucose steadily for over more hours, is given. For children, 1.6 grams of cornstarch per kilogram is given; for older children and adults, 1.7 to 2.5 gm of cornstarch per kilogram of body weight is given.

• A lactate meter is used as a medical alert tool to alert the parents of very young patients.

• This tool will give an immediate indication of low glucose levels. During emergencies, cornstarch, glucose polymers, and glucose tablets used by diabetics are used, which will release glucose quickly.

• To manage lactic acidosis, oral citrate or bicarbonate is given to alkalinize the urine and prevent the formation of hard deposits in the kidney, called urolithiasis and nephrocalcinosis. To avoid the risk of gout, allopurinol is given. Colchicine is preferred during an acute attack of gout.

• A set of lesions can develop in the liver, including hepatocellular carcinoma, hepatocellular adenoma, fatty infiltration, and localized hyperplasia. A liver function test should be done once every 6 to 12 months. When the liver fails to respond to initial treatments, liver transplantation is a treatment choice.

What Complications Does Von Gierke Disease Cause?

• Bleeding disorder.

• Osteoporosis.

• Increased risk of bone fracture.

• Atherosclerosis.

• Acute pancreatitis.

• Gout.

• Polycystic ovarian syndrome.

• Crohn's disease.

• Hypothyroidism.

Conclusion:

Generally, patients affected with this genetic disorder who receive appropriate treatment live with normal life expectancies. But there have been cases of death during infancy without timely and suitable treatment for metabolic disturbances. There is limited physical and intellectual maturity due to low glucose levels. So the child will need special care. Their physician should regularly check them.