Glycogen storage disease type III

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at January 6, 2017
StartDiseasesGlycogen storage disease type III

Glycogen storage disease type III or GSD III is an inherited disease stemming from genetic abnormalities that prevent the process by which glycogen is broken down by the body. It is associated with a wide variety of symptoms and affects the liver, skeletal muscles, and cardiac muscle. It is a type of glycogen storage disease.

Contents

Definition & Facts

A patient presenting with glycogen storage disease type III has an inability to produce functional glycogen debranching enzyme. In an individual without GSD III, this enzyme circulates in the blood and is responsible for breaking down glycogen. Glycogen is the body's main method of storing glucose in the body, otherwise known as blood sugar, which is the primary fuel for the human body.

In an individual with GSD III, the enzyme that are responsible for breaking down the glycogen in the bloodstream have genetic mutations that prevent them from performing their function correctly, which means that blood sugar is at deficient levels.

The body will release the hormones, adrenaline and glucagon to counteract the low level of glucose in the bloodstream. Without enough blood sugar, the body lacks the energy to perform routine tasks and a wide variety of symptoms will manifest. In addition, there will be a surplus of abnormal glycogen in the bloodstream which contributes to symptoms.

Symptoms & Complaints

There are many symptoms that are associated with glycogen storage disease type III. Hypoglycemia or low blood sugar can begin as soon as the child with this condition is born and can alter the functioning of the central nervous system.

The symptoms of a hypoglycemic reaction include: shaking and palpitations of the heart; sweating and clammy skin; headache; hunger and/or nausea; impaired thinking, mood swings, and personality changes; fatigue; loss of coordination and slurred speech; and even coma and seizures.

GSD III also causes an enlarged, swollen liver and an enlarged, swollen heart. The muscles of the patient may be weak and begin to waste away over time, and if the patient is a child, they may not experience an appropriate amount of growth that is expected for their age group. Developmental delays in motor functioning may also occur.

Women may have polycystic ovaries though they usually do not become infertile as a result.

Causes

The cause of glycogen storage disease type III is genetic. Specifically, it occurs when there is a mutation in the gene that is responsible for creating the glycogen debranching enzyme necessary for breaking down glycogen. This gene is the AGL gene.

Both parents need to be a genetic carrier of this mutation in order for it to be passed down to the child, as the mutation is recessive and autosomal; that is, the genes involved do not exist on a sex chromosome and so every person has two copies of it, which means that as long as an individual has at least one gene without the mutation, they will be able to produce functional glycogen debranching enzyme.

Diagnosis & Tests

In order to diagnose glycogen storage disease type III, there are different methods that a health care provider can use. One diagnostic method is to perform a biopsy of the liver and/or the muscles to see if excess glycogen is accumulating within. Another diagnostic method is to perform an ultrasound of the liver which can detect abnormalities such as the liver being enlarged. Other imaging studies could include computed tomography (CT) scans of the liver.

In addition, the health care provider will order a complete blood count, which is a blood test that gives a detailed accounting of the cells that are within the patient's blood. This is a way for a physician to measure the level of glycogen in the blood and to analyze the glycogen debranching enzyme, in addition to verifying the existence of low blood sugar. DNA mutation analysis is another diagnostic tool. This test serves to confirm a suspected diagnosis of GSD III and to discover what specific subtype the patient is carrying.

Liver enzyme tests should be conducted as should tests which examine the quantity and quality of lipids in the blood. Echocardiograms and electrocardiograms may be conducted to examine heart problems that can result from this condition.

Treatment & Therapy

Glycogen storage disease type III is a genetic disorder, and it can be managed but not cured. This disorder involves controlling the diet to prevent hypoglycemia. Nasogastric tube feeding will need to be provided at night so that hypoglycemia does not set in. Cornstarch plays an important role in the diet, allowing blood glucose levels to stay at a healthy level for a period of time.

Glucagon can be administered to stimulate gluconeogenesis. Another way to manage GSD III is by administering glucose directly into the bloodstream by means of intravenous therapy, or IV.

Physical therapy is advised for those patients that suffer from impaired muscle and motor skills functioning. Sometimes the symptoms of GSD III can hinder everyday activity such as typing, walking, driving, and all manner of activities that require dextrous use of the patient's hands. Thus physical therapy can help strengthen any weakened muscles and bones that have been identified in the patient.

Prevention & Prophylaxis

While glycogen storage disease type III cannot be prevented, it is possible to determine whether one is a carrier of the gene mutations involved through genetic analysis techniques.

Those who suffer from GSD III most often live to adulthood and beyond. While the liver enlargement typical of child patients disappears during adolescence, adult patients may experience liver, heart or muscle problems as they age. For this reason, monitoring is advised to track the progression of adverse symptoms related to GSD III.