OVERVIEW Glycogen storage disease type I (also known as GSDI or von Gierke disease) is an inherited disorder caused by the

buildup of a complex sugar called glycogen in the body's cells. The accumulation of glycogen in certain organs and tissues, especially the liver, kidneys, and small intestines, impairs their ability to function normally. This condition is inherited in an autosomal recessive pattern where parents of an individual with an autosomal recessive condition typically do not show signs and symptoms of the condition.

CAUSES Mutations in two genes, G6PC cause GSDIa. SLC37A4 cause GSDIb. This gene codes for the protein glucose-6-phosphate transporter.

The proteins produced from the G6PC and SLC37A4 genes work together to break down a type of sugar molecule called glucose 6-phosphate. The breakdown of this molecule produces the simple sugar glucose, which is the primary energy source for most cells in the body. Mutations in the G6PC and SLC37A4 genes prevent the effective breakdown of glucose 6phosphate. Glucose 6-phosphate that is not broken down to glucose is converted to glycogen and fat so it can be stored within cells.

Too much glycogen and fat stored within a cell can be toxic. This buildup damages organs and tissues throughout the body, particularly the liver and kidneys, leading to the signs and symptoms of GSDI.

Symptoms

Symptoms include the following:

Tremors Irritability Cyanosis Seizures Apnea Coma

Older infants may present with the following: Frequent lethargy Difficult arousal from overnight sleep Tremors Overwhelming hunger Poor growth Apparent increase in abdominal girth, although extremities appear thin

Pathophysiology

In the hepatocyte, the glycogen catabolic machinery normally responds to stimuli caused by hypoglycemia (eg, neural, hormonal), ending in a flood of glucose-6-phosphate that cannot be released from the cell. However, glucose-6-phosphate is also the substrate for glycolysis and produces lactate. Lactate exits the hepatocyte, causing clinically significant lactic acidemia in proportion to the degree of stimulus for glycogen breakdown. The accumulation of lactic acid in blood can cause true acidosis with a large anion gap, a characteristic of glycogen-storage disease type I.

Diagnosis
Laboratory Studies
Measuring blood glucose levels with electrolytes- if the blood glucose concentration is low, measurement of electrolyte levels may permit calculation of an increased anion gap, which suggests lactic acidemia. Measurement of liver function, plasma uric acid levels, and urinary creatinine clearance are essential.

Perform a CBC count and differential. In patients with glycogen-storage disease type Ia, the WBC count is usually within reference ranges because the defect does not affect leukocyte function. In contrast, glycogen-storage disease Ib causes chronic granulocytopenia due to the impaired function of the neutrophils, particularly in relation to gram-positive organisms. Perform a coagulation profile to include bleeding time tests.

Imaging Studies
Ultrasonography of liver and kidneys. Abdominal ultrasonography can enable reasonable estimates of liver and kidney size- especially useful during treatment of patients with chronic glycogen-storage disease because the relative size of the liver is expected to diminish with growth of the child. Ultrasonography provides a baseline for evaluating nodules. Bone-density studies in middle childhood to identify patients who may have diminished bone density in adolescence.

Treatment

Avoid high lipid intake for triglyceridemia Avoid excessive carbohydrates and calories while supplying adequate calories and protein for growth. Glycogen-storage disease type Ia (GSD Ia) has no specific medication requirement beyond prophylactic PO iron and prompt treatment of intercurrent infections (which may interrupt PO intake).

Medication
Trace Elements- These are inorganic substances found in small amounts in the tissues and required for various metabolic processes. Iron sulfate (feosol)- Nutritionally essential inorganic substance.

Colony stimulating factors- These agents act as hematopoietic growth factors that stimulate the development of granulocytes. These drugs are also used to mobilize autologous peripheral blood progenitor cells for bone marrow transplantation and to manage chronic neutropenia. Filgrastim (G-CSF, Neupogen)- activates and stimulates production, maturation, migration, and cytotoxicity of neutrophils.

Surgery is usually unnecessary after initial diagnosis using open liver biopsy.