Glycogen Storage Disease Type IV
Glycogen Storage disease type IV (GSD-IV) belongs to a group of rare genetic disorders of metabolism, known as “glycogen storage diseases.” GSD-IV may also be referred to as:
- Andersen Glycogenosis
- Brancher Deficiency
- Glycogen Storage Disease IV
- Glycogenosis Type IV
- Branching Enzyme Deficiency
What is Metabolism?
Metabolism is a process by which food is broken down and converted into energy and other products that are needed by the body. This is a series of complex step by step processes, and often the food we eat is changed into many different forms before the body’s cells are able to use it to make energy. Metabolism is controlled by enzymes, which are natural proteins (or chemicals) in the body that help speed up the process. When one or more chemicals aren’t present or working properly in the body, that individual is not able to break down food, which then affects the amount of energy available to the cells in the body. Inside each cell of our bodies, there are structures known as mitochondria, which could be called the cell’s “engines.” Metabolic diseases, such as GDS-IV, are caused by problems in the way certain fuel molecules are processed before they enter the mitochondria, or by the inability to get fuel molecules into mitochondria, resulting in the mitochondria being unable to produce energy (or ATP).
Metabolic disorders can affect all the body’s voluntary muscles, such as those in the arms, legs and trunk. The heart, liver and kidneys can also be damaged.
What is GSD-IV?
In GSD-IV, glycogen (a type of carbohydrate) is not able to be converted into a sugar called glucose, which the cells need to use as energy. This is due to a loss of activity of specific enzyme, known as glycogen-branching enzyme, resulting in the altered glycogen build-up in the liver, muscle, and/or other tissues. The build-up of glycogen in the cells causes progressive damage to the cells, which leads to the cell to not being able to function properly. Therefore the cell is unable to produce the energy it needs.
Many individuals who are affected with GSD-IV experience symptoms in the first months of life. Such features typically include failure to grow and gain weight at the expected rate (failure to thrive) and abnormal enlargement of the liver and spleen (hepatosplenomegaly). In such cases, the disease course is typically characterized by progressive liver scarring (cirrhosis) and liver failure, leading to potentially life-threatening complications. In rare cases, however, progressive liver disease may not develop. The muscles and heart can also be affected.
There are however, a small number of individuals who do not experience symptoms until later in life.
What is the cause of GSD-IV?
GSD-IV is caused by a specific gene change that can be passed on through a family. A gene is a “recipe” or set of instructions for making a protein, such as an enzyme. A change in the gene may cause the enzyme to be made incorrectly or not at all, leading to a deficiency in the amount of that enzyme in the body.
For a child to have GSD-IV, both healthy parents must have one altered gene each, which they both pass onto their child. As we each have two copies of each gene, one altered copy of a gene is not enough to cause symptoms as there is a ‘back up’ copy of that gene. If both parents pass on their altered gene copy to their child, the child will have inherited 2 altered copies and therefore have no ‘back up’ copy to produce the enzyme. This is known as autosomal recessive inheritance (see below).
It is important to remember that this is something that you cannot control and would not know about until you have an affected child.
What is the treatment for GSD-IV?
Although there is no ‘cure’ for GSD-IV, there are some treatments that may be considered. These treatments surround the complications that occur with the liver and are treated symptomatically. In some cases, a liver transplant may an option, however, the heart and muscles may still be affected.
How is GSD-IV diagnosed?
It’s important to get an accurate diagnosis. Because these diseases are rare, many people spend some time trying to find out what caused their symptoms. The diagnostic process usually begins with a careful medical history, a physical exam and a neurological exam to test reflexes, strength and the distribution of weakness.
Several specialized tests are used to confirm a suspected diagnosis of metabolic disease:
- Blood tests can be used to detect the presence of certain chemicals in the blood that may indicate some metabolic diseases.
- An exercise test is used to monitor a person’s response to intense or moderate exercise. Blood samples are taken during exercise for testing.
- Electromyography (EMG) uses small needle electrodes to measure the electrical currents in a muscle as it contracts. While an EMG can’t definitively diagnose metabolic disease, it can be used to rule out a number of other types of neuromuscular disease that cause similar patterns of weakness.
- A muscle biopsy requires the removal of a small piece of muscle tissue for microscopic analysis. The procedure is done either surgically, with an incision to expose the target muscle, or with a needle. A skin biopsy is also sometimes performed.
- Other tests that may be needed include an electrocardiogram to test heart function, and brain imaging studies such as CT or MRI scans.
- Genetic tests, using a blood sample, can analyse the person’s genes for particular defects that cause metabolic disease, but these tests often aren’t necessary for diagnosis or for determining treatment.
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