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Madisons Foundation - Moms And Dads In Search Of Needed Support
Glycogen Storage Disease Type 1B
GSD1B, glucose-6-phosphate transport defect)
Wednesday, 27 July 2005
Last Updated Wednesday, 27 July 2005
What
Glycogen storage disease type 1b is an autosomal recessive genetic disorder classified as an inborn error of glycogen metabolism. It occurs because a protein, called glucose-6-phosphate transporter (G6P transporter), does not function properly due to a mutation in the gene that encodes it. The consequence of this is that glucose, our main source of energy, which is stored in the cells of the liver, is not released into the blood and cannot be used. Hence, many of the body’s processes lack energy and are impaired. People with GSD1B also show low levels of leukocytes and leukocyte impairment. Leukocytes are white blood cells that are part of the immune system. Since they are impaired, people with GSD1B experience recurrent infections.Who
Children with GSD1B usually present with symptoms early in life. Children typically range in age from one day to 4 years old. The majority of children present before one year of age. The incidence of GSD1B is approximately 1/100,000 children.Signs and Symptoms
Most patients experience the following dominant symptoms: - protruding abdomen due to enlarged liver from increased glycogen storage - low blood sugar, sometimes so low as to cause seizures or coma - growth failure, short stature, delayed puberty - high cholesterol, high blood triglycerides, high blood levels of uric acid: These conditions can lead to the formation of yellow plaques or nodules on the skin, as well as cause inflammation of the pancreas. - recurrent infections, commonly around the mouth and anus, due to a low number of white blood cells - weak bones, fractures - kidney disease - muscle weakness Other symptoms are: - delayed psychomotor development - inflammatory bowel disease - anemia - nosebleeds - benign tumors in the liver - cysts in the ovaries - altered brain function and structure possibly due to low blood sugar episodes - pulmonary hypertension (high blood pressure in the lungs’ vessels) resulting in shortness of breathPossible Causes
In GSD1B the mutation is located in the glucose-6-phosphate transporter gene, which is on chromosome 11. This gene codes for the protein glucose-6-phosphate transporter. The body stores glucose in the form of glucose chains called glycogen. Although there are many places in the body where glycogen is stored, the liver is the organ richest in glycogen. During periods when the blood glucose becomes low, the liver will release glucose into the blood by breaking-down glycogen. Break-down of glycogen occurs in steps that require many enzymes and other proteins. One of these steps involves the transport of glucose-6-phosphate (G6P), a precursor to glucose, to move from the cell’s cytoplasm into a compartment of the cell called the endoplasmic reticulum. Normally, G6P is transported by the protein G6P transporter, but since people with GSD1B have a defective G6P transporter, G6P stays in the cell’s cytoplasm and it is not converted into glucose. The exact cause of the neutropenia and neutrophil dysfunction (low white blood cell count and impaired white blood cell function) are yet unknown.Diagnosis
Glycogen storage disease type 1 is suspected when patients present with acidic blood, low blood sugar, high concentration of lipids in the blood and an enlarged liver. The first step in confirming the diagnosis is DNA testing for common mutations. If none is identified, a liver biopsy is performed. The biopsy shows increased glycogen storage in the liver cells as well as fatty deposits. enzyme analysis for glucose-6-phosphate transporter activity shows low activity and it can also be used to determine the diagnosis.Treatment
The main goal of treatment is to maintain appropriate blood glucose levels while still avoiding the excess storage of glycogen. There are drugs to treat the high levels of uric acid in the blood, to preserve kidney function, and improve glucose control. Treatment with granulocyte colony stimulating factor (G-CSF), and granulocyte macrophage colony stimulating factor (GM-CSF) increases the level of white blood cells. Glucose concentrations can be maintained with frequent administration of uncooked cornstarch. Cornstarch is a carbohydrate that slowly breaks down into glucose, thus providing the body with a slow rate of blood sugar. This prevents the body from storing the excess glucose as glycogen. Some children use a nasogastric tube (a tube that goes down the nose and into the stomach) at night to supply the body with sugar during sleep. A diet high in protein is not recommended and certain carbohydrates, such as lactose, galactose, fructose and sucrose, should be avoided since they can be converted and stored as glycogen quite readily.Prognosis
Currently, there is no cure for GSD1B and the signs and symptoms continue into adulthood. Older children and adults often develop liver adenomas that undergo malignant transformation in approximately 10 percent of cases. Recent data shows that treatment with G-CSF or GM-CSF reduces the incidence of recurrent infections. With proper treatment consisting of appropriate drugs and diet children can have a healthy life expectancy.Connect with other parents
In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.Weblinks
Association of Glycogen Storage Disease
This organization has more information about glycogen storage diseases, has additional links and has an email list sign-up.
The Children’s Fund for GSD Research
This organization provides information on glycogen storage disease and also provides financial support for research on this disorder.
Neutropenia Support Association Inc.
This organization provides more information about living with a low count of white blood cells and provides links for more information and support groups.