Glycogen storage disease type I
Glycogen storage disease type I, or GSDI is a disease where the liver can’t convert glycogen into glucose but allows it to accumulate in the organs and tissues. Glycogen is a complex sugar that’s stored in the liver and kidneys until the body needs energy in the form of glucose.
Definition & Facts
The build-up of glycogen hampers the ability of organs like the small intestines, liver, and kidneys to function the way they should. Glycogen storage disease type I also inhibits the liver from performing gluconeogenesis, where glucose is produced from the breakdown of proteins and other substances that are not carbohydrates.
The problem is seen in about 1 in 50,000 to 1 in 100,000 live births, though the incidence is 1 in 20,000 among Ashkenazi Jews. The risk of inheriting the disease is about the same for boys and girls. It is caused by genetic mutations inherited from both parents, and symptoms appear in infancy.
Symptoms & Complaints
- Failure to thrive
- Enlarged liver (hepatomegaly) and distended abdomen
- Enlarged kidneys
- Hunger that can’t be satiated
- Clammy skin
- Vomiting that may lead to dehydration
- Rapid breathing
Children with GSDI often have a short stature, thin arms and legs, and plump cheeks. Their bones may become weak from osteoporosis, and they may suffer from gout, which is a build up of uric acid in their joints.
They may have xanthomas and suffer from diarrhea. Xanthomas are fatty deposits just under their skin. They can grow anywhere on the body but are usually found around the child’s joints. Some patients have frequent nosebleeds due to impairment in the way their blood platelets function.
People with GSDI often have elevated pressure in the blood vessels that serve their lungs. This is called pulmonary hypertension. As adults, years of kidney damage puts them at risk for kidney failure. GSDI patients achieve puberty later than normal, and girls may have polycystic ovaries.
Tumors called adenomas may appear in their livers because of the lack of the enzyme needed to convert glycogen into glucose. Adenomas are often benign but can become malignant. However, the liver is able to carry out most of its other functions normally in a patient who has glycogen storage disease type I.
There are two types: GSDIa and GSDIb. Most people with GSDI have the Ia type, but patients who suffer from GSDIb have low levels of white blood cells, a condition called neutropenia. Because white blood cells are part of the immune system, these patients are at risk for repeated bacterial infections. They are prone to inflammations of their gums (gingivitis), dental cavities, and mouth ulcers. They may suffer from inflammatory bowel disease.
GSDI is caused by genetic mutations in the G6PC gene and SLC37A4 genes. Together, these genes help to break down a more complex sugar molecule into simple glucose. In a person with GSDI, this sugar molecule, glucose-6-phosphate, is not broken down into glucose by the enzyme glucose-6-phosphatase but is turned to glycogen and fat. These substances accumulate in the cells and damage them.
For a child to inherit the disease, they must get a defective gene from both parents. This is called an autosomal recessive inheritance. Usually, the parents do not have the condition themselves but are genetic carriers.
Diagnosis & Tests
GSDI is diagnosed with blood tests that reveal abnormal levels of cholesterol, glucose and triglycerides in the blood. The doctor orders genetic tests for a positive diagnosis of GSDI and imaging tests such as ultrasound for the child’s liver and kidneys. The doctor may also take a liver biopsy, which can reveal the deficient enzyme in glycogen storage disease type I.
Treatment & Therapy
Children with GSDI are put on a special diet. They may be fed raw cornstarch in water because the body digests cornstarch slowly. This allows glucose to be delivered continuously but not overwhelmingly. The child may also be fed soy milk or formula made of soy.
They may need to wear a nasogastric tube overnight and be fed small, frequent, carbohydrate-rich meals throughout the day to stimulate the slow and steady release of glucose. Sugars such as fructose need to be restricted, but doctors are not in agreement as to how much.
Medications that are used to treat GSDI include allopurinol, which lowers the levels of uric acid in the system. This helps to ease the pain of gout in teenaged patients. Patients who have repeated infections can be treated with human granulocyte colony-stimulating factor or GCSF. The doctor prescribes drugs that lower the levels of fats in the blood and treat kidney disease. Adenomas can be removed through surgery or radiofrequency ablation if it is feared they will become malignant or bleed.
As a last resort, GSDI patients may be recommended to have a kidney transplants or liver transplant if other treatments fail. Patients with GSDI need to be monitored by their physicians, which includes ultrasounds of the liver and kidney and blood tests yearly.
Prevention & Prophylaxis