Summary about Disease
Glycogen storage disease type I (GSD I), also known as Von Gierke disease, is a rare genetic metabolic disorder caused by a deficiency in the enzyme glucose-6-phosphatase (G6Pase) or its transporter. This enzyme is crucial for releasing glucose from glycogen in the liver, kidneys, and intestines. The deficiency prevents the breakdown of glycogen into glucose, leading to an accumulation of glycogen in these organs and a buildup of other metabolites. This results in hypoglycemia (low blood sugar) and other metabolic abnormalities.
Symptoms
Common symptoms include:
Hypoglycemia (low blood sugar), especially between meals or overnight
Hepatomegaly (enlarged liver)
Nephromegaly (enlarged kidneys)
Growth retardation and delayed puberty
Lactic acidosis (buildup of lactic acid)
Hyperlipidemia (high levels of fats in the blood)
Hyperuricemia (high levels of uric acid in the blood) leading to gout
Protuberant abdomen (enlarged abdomen due to enlarged liver and kidneys)
Osteoporosis
Nosebleeds (due to platelet dysfunction)
Causes
GSD I is caused by mutations in genes that encode for glucose-6-phosphatase (G6Pase) or its transporter. The most common type, GSD Ia, is caused by mutations in the G6PC gene, which provides instructions for making G6Pase. GSD Ib is caused by mutations in the *SLC37A4* gene, which encodes the glucose-6-phosphate transporter. These mutations are inherited in an autosomal recessive pattern, meaning both parents must carry a copy of the mutated gene for a child to be affected.
Medicine Used
There is no cure for GSD I, so treatment focuses on managing the symptoms and preventing complications. The main treatment strategies involve:
Dietary Management: Frequent feeding of small meals and snacks, especially those high in complex carbohydrates. Uncooked cornstarch is often used as a slow-release source of glucose.
Continuous nocturnal gastric drip feeding: Providing a constant supply of glucose overnight to prevent hypoglycemia.
Allopurinol: To reduce uric acid levels.
Statins/Fibrates: To manage hyperlipidemia.
Granulocyte colony-stimulating factor (G-CSF): For GSD Ib patients with neutropenia (low white blood cell count).
Kidney and/or Liver transplant: In severe cases with complications, transplantation may be considered.
Is Communicable
No, Glycogen storage disease type I (Von Gierke) is not communicable. It is a genetic disorder and cannot be spread from person to person.
Precautions
Precautions for individuals with GSD I and their caregivers include:
Strict adherence to dietary plan: Meticulously follow the prescribed diet to maintain blood glucose levels.
Regular blood glucose monitoring: Frequent monitoring of blood glucose levels is essential.
Emergency glucagon kit: Have a glucagon kit available for emergency treatment of severe hypoglycemia.
Avoiding fasting: Patients should never fast for prolonged periods.
Managing infections promptly: Infections can worsen metabolic abnormalities.
Regular medical check-ups: Regular visits to a metabolic specialist are crucial.
Genetic counseling: For families with a history of GSD I.
How long does an outbreak last?
GSD I is not an infectious disease and does not involve outbreaks. It is a chronic, lifelong condition that requires continuous management. Hypoglycemic episodes can occur acutely if the dietary plan is not followed.
How is it diagnosed?
Diagnosis typically involves:
Newborn Screening: Some states include GSD I in their newborn screening programs, which can detect the disease early.
Physical Examination and History: Evaluation of symptoms and family history.
Blood Tests: Measurement of blood glucose, lactate, uric acid, triglycerides, and liver enzymes.
Enzyme Assay: Measurement of glucose-6-phosphatase activity in a liver biopsy sample.
Genetic Testing: DNA analysis to identify mutations in the G6PC or *SLC37A4* genes.
Liver Biopsy: To examine liver tissue for glycogen accumulation and to measure enzyme activity.
Timeline of Symptoms
Infancy: Symptoms often manifest in infancy, typically within the first few months of life, with hypoglycemia, hepatomegaly, and lactic acidosis.
Childhood: Growth retardation and delayed puberty become apparent. Hyperlipidemia and hyperuricemia may develop.
Adulthood: If not properly managed, complications such as hepatic adenomas, kidney disease, pulmonary hypertension, and gout can occur.
Important Considerations
Early diagnosis and management are crucial to prevent complications and improve long-term outcomes.
Lifelong adherence to a strict dietary regimen is essential.
Regular monitoring by a metabolic specialist is necessary to adjust treatment as needed.
Patient education and support are vital for successful disease management.
Genetic counseling is recommended for families with a history of GSD I to assess recurrence risk and provide information about reproductive options.
Emerging therapies such as gene therapy are being investigated as potential future treatments.