The differential diagnosis list includes glycogenoses types III and VI, fructose 1,6-bisphosphatase deficiency, and a few other conditions (page 5), but none are likely to produce all of the features of GSD I. The next step is usually a carefully monitored fast. Hypoglycemia often occurs within six hours. A critical blood specimen obtained at the time of hypoglycemia typically reveals a mild metabolic acidosis, high free fatty acids and  beta-hydroxybutyrate, very low insulin levels, and high levels of glucagon, cortisol, and growth hormone. Administration of intramuscular or intravenous glucagon (0.25 to 1 mg, depending on age) or epinephrine produces little rise of blood sugar. The diagnosis is definitively confirmed by liver biopsy with electron microscopy and assay of glucose-6-phosphatase activity in the tissue and/or specific gene testing, available in recent years. Treatment
The primary treatment goal is prevention of hypoglycemia and the secondary metabolic derangements by frequent feedings of foods high in glucose or starch (which is readily digested to glucose). To compensate for the inability of the liver to provide sugar, the total amount of dietary carbohydrate should approximate the 24-hour glucose production rate. The diet should contain approximately 65–70% carbohydrate, 10–15% protein, and 20–25% fat. At least a third of the carbohydrates should be supplied through the night, so that a young child goes no more than 3–4 hours without carbohydrate intake. Once a diagnosis is made, the priority in GSD I treatment is to maintain an adequate blood glucose.
Severity of platelet dysfunction typically correlates with clinical condition, with the most severe cases correlating with lactic acidosis and severely lipidemia. It may cause clinically significant bleeding, especially epistaxis. Additionally, GSD I patients may present with thrombocytopenia as a consequence of splenomegaly. In the setting of splenomegaly various hematologic factors may be sequestered in the tissues of the spleen as blood is filtered through the organ. This can diminish levels of platelets available in the bloodstream, leading to thrombocytopenia. Developmental effects
Developmental delay is a potential secondary effect of chronic or recurrent hypoglycemia, but is at least theoretically preventable. Normal neuronal and muscle cells do not express glucose-6-phosphatase, and are thus not impacted by GSD I directly. However, without proper treatment of hypoglycemia, growth failure commonly results from chronically low insulin levels, persistent acidosis, chronic elevation of catabolic hormones, and calorie insufficiency (or malabsorption). The most dramatic developmental delays are often the cause of severe (not just persistent) episodes of hypoglycemia. Diagnosis
Several different problems may lead to the diagnosis, usually by two years of age:

seizures or other manifestations of severe fasting hypoglycemia
hepatomegaly with abdominal protuberance
hyperventilation and apparent respiratory distress due to metabolic acidosis
episodes of vomiting due to metabolic acidosis, often precipitated by minor illness and accompanied by hypoglycemiaOnce the diagnosis is suspected, the multiplicity of clinical and laboratory features usually makes a strong circumstantial case. If hepatomegaly, fasting hypoglycemia, and poor growth are accompanied by lactic acidosis, hyperuricemia, hypertriglyceridemia, and enlarged kidneys by ultrasound, GSD I is the most likely diagnosis.