Glycogen Storage Disorders

What is glycogen?

Your body needs the sugar glucose to provide energy so that your cells and organs can function normally. Glucose is stored in your muscles and liver as a substance called glycogen. Glycogen is essentially made up of a number of glucose molecules (units) joined together. Various different proteins, known as enzymes, help to convert glucose into glycogen for energy storage. Other enzymes break down the glycogen back into glucose when more glucose is needed for energy. Metabolism is the name given to the process that results in the production of energy in the body.

What are glycogen storage disorders?

Glycogen storage disorders are a group of inherited diseases that result from a lack of, or abnormal functioning of, one of the enzymes involved in the conversion of glucose to glycogen or the breakdown of glycogen back into glucose. Because there are a number of different enzymes involved in glycogen production and breakdown, there are a number of different glycogen storage disorders. In fact, there are over 12 types of glycogen storage disorder. Each disorder has a different enzyme lack or malfunction.

If the enzyme problem is with one of the enzymes involved in glycogen synthesis (production), this causes reduced amounts of 'normal' glycogen to be produced and sometimes 'abnormal' glycogen is produced.

If the enzyme problem is with one of the enzymes involved in glycogen breakdown back into glucose, this can lead to :

• Low levels of glucose in your body (a condition known as hypoglycaemia).
• A build-up of glycogen in your muscles and liver.

Because glycogen storage disorders are inherited and can affect energy production and metabolism within your body, they are also known as inborn errors of metabolism.

What are the different types of glycogen storage disorders?

Glycogen storage disorders are classified according to which enzyme is lacking or not working normally and also which part of the body is affected by the disease. Glycogen storage disorders mostly tend to affect your liver and muscles. However, some glycogen storage disorders can affect other parts of the body such as the kidney, heart, blood vessels, nervous system and bowel (see below).

Type I glycogen storage disorder is the most common. About one quarter of people who have glycogen storage disorder have Type I. It is due to a lack of the enzyme known as glucose-6-phosphatase.

The different types of glycogen storage disorder include:

• Type Ia (Von Gierke's disease), Type Ib, Type Ic, Type Id
• Type II (Pompe's disease)
• Type III (Forbes-Cori disease)
• Type IV (Andersen's disease)
• Type V (McArdle's disease)
• Type VI (Her's disease)
• Type VII (Tarui disease)
• Type VIII
• Type IX
• Type X
• Type 0 (Lewis disease)

Who gets glycogen storage disorders?

Glycogen storage disorders are rare. It is estimated that about one in every 20,000 to 40,000 babies born has a glycogen storage disorder. Glycogen storage disorders are inherited. This means that they are passed on in families through your genes.

Autosomal recessive inheritance pattern

Most, but not all, glycogen storage disorders are inherited in a pattern called autosomal recessive inheritance.

X-linked inheritance pattern

This occurs in glycogen storage disorder Type VI, and some people with Type IX.

What are the symptoms of glycogen storage disorders?

Some disorders affect the liver (Types I, IV, VI & IX), some the muscles (Types V & VII) and some both (Type III). Disorders affecting the liver lead to liver enlargement and can be associated with a tendency to a low blood sugar. Those affecting the muscles cause muscle weakness and sometimes kidney disease.

Glycogen storage disorders are usually first diagnosed in babies and children. The common features, particularly for Type I, include:

• Abnormally slow growth which may be detected by your child's health visitor or GP on routine examination.
• Low blood sugar levels which can cause symptoms such as sweating, tremor, drowsiness, confusion and sometimes convulsions.
• An enlarged liver which a doctor may feel when they examine your child's abdomen.
• Noticeably weaker muscles. This can mean that your baby can appear 'floppy' when they are held.
• Obesity.
• Problems with bleeding and blood clotting.
• Kidney problems.

In teenagers and adults, glycogen storage disorders usually cause fatigue (tiredness), feeling weak when exercising, or the feeling of aching and weak muscles.

Some glycogen storage disorders, particularly Type Ib, Ic and Id, can affect your immune system and make you more susceptible to infections.

Glycogen storage disorder Type II can affect your heart, muscles, liver, nervous system and blood vessels. In babies, this can lead to breathing problems, muscle weakness and abnormal enlargement of the heart. This means that the heart cannot function normally which can lead to heart failure. In teenagers and adults, glycogen storage disorder Type II can lead to muscle weakness in the limbs but also weakness of the muscles that are used to help your breathing. This can lead to difficulty breathing and respiratory failure.

How are glycogen storage disorders diagnosed?

Glycogen storage disorders can run in families. There may already be a history in your family of a glycogen storage disorder which may mean that your doctor suggests that you or your child are tested.

If your doctor suspects that you or your child may have a glycogen storage disease, they may suggest the following investigations:

Blood tests

These may include testing your blood sugar levels, which may be low, and also blood tests to look at your kidneys and liver. A special blood test called creatine kinase can give your doctor information about whether the glycogen storage disorder is affecting your muscles.

Other blood tests may include checking your blood count to look for anaemia and a test of your blood clotting.

Scans

An abdominal ultrasound scan can show if the glycogen storage disorder is causing enlargement of your liver. This is a painless test. It is the same type of scan that pregnant women have to look at the baby in the womb. Some gel is spread onto your abdomen. The ultrasonographer then moves the scanning probe over the surface of your abdomen. High-frequency sound waves allow them to produce an image of the inside of your abdomen that they can look at. Your doctor may also suggest a special ultrasound scan of your heart called an echocardiogram. This is because certain types of glycogen storage disorders can cause heart problems.

Biopsy

Your doctor may suggest that they take a biopsy (a sample of tissue) either from one of your muscles or from your liver. The tissue sample will be sent to the laboratory for tests and an examination under the microscope. The levels of glycogen and fat in the tissue can be measured as well as the levels of enzymes present. This can help to confirm the type of glycogen storage disorder.

Other tests

Other tests are sometimes carried out depending on the type of glycogen storage disorder that your doctor suspects.

What are the treatment options for glycogen storage disorders?

The treatment for glycogen storage disorders varies depending on which disorder you have. With most, the treatment aims are to stabilise your blood sugar and energy levels within your body. This is normally achieved by using nutritional supplements such as glucose, either via a drip into your veins, or via a nasogastric tube (a tube that is passed through your nose into your stomach). When things become more stable, supplements can be taken by mouth. A high protein diet is also helpful in some glycogen storage disorders.

Some people with glycogen storage disorders who do not respond to nutritional supplements need a liver transplant. People with glycogen storage disorders affecting their immune system may need to take regular antibiotics to protect against infection.

In some glycogen storage disorders, clinical trials have successfully used treatment involving replacement of the enzymes that are deficient or not working normally. For example, in glycogen storage disorder Type II, this treatment has been shown to help reverse the heart problems and muscle weakness that can occur.

Other clinical trials are underway that are looking at gene therapy as a treatment. This is where doctors and scientists aim to cure genetic diseases by introducing 'normal' genes into patients to overcome the effects of 'faulty' genes, using techniques of genetic engineering.

What is the outlook (prognosis) for glycogen storage disorders?

The outlook depends on the type of glycogen storage disorder that you have. Some glycogen storage disorders have a better outlook than others and do not affect life expectancy. However, some glycogen storage disorders are more severe and because of their effects on muscles, your liver and your heart, can lead to problems with breathing and heart function. This can sometimes lead to death which can occur at a very early age in some cases.

Your doctor will be able to discuss the outlook for a particular glycogen storage disorder in more detail. The possibility of new treatments and therapies are constantly emerging. Enzyme replacement therapy and gene therapy mean that, hopefully, the outlook for glycogen storage disorders will soon be greatly improved.

Can glycogen storage disorders be prevented?

Glycogen storage disorders are hereditary conditions that run in families. If someone else in your family, or if you yourself, 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.

Further help and information

The Association for Glycogen Storage Diseases (UK)

9 Lindop Road, Hale, Altrincham WA15 9DZ
Tel: 0161 980 7303
Web: www.agsd.org.uk
Offers support for affected individuals and families and linking of families where possible. Can provide information about current treatments and long term prospects for people with glycogen storage disorders.

Contact a Family

209-211 City Road, London EC1V 1JN
Tel (Family Advice Helpline): 0808 808 3555 Tel (Minicom): 0808 808 3556
Web: www.cafamily.org.uk
Has the primary aim of encouraging mutual support between families of disabled children.