However, continuing research has revealed that these clinical features are the consequences of only one (in GSD Ia) or two (in GSD Ib) fundamental abnormalities:

impairment in the livers ability to convert stored glycogen into glucose through glycogenolysis
in GSD Ib, impairment of the neutrophils ability to take up glucose, resulting in neutrophil dysfunction and neutropeniaThese fundamental abnormalities give rise to a small number of primary clinical manifestations, which are the features considered in diagnosis of GSD I:

Low blood sugar (hypoglycemia), due to impairment of glycogen breakdown (glycogenolysis) causing insufficient fasting blood glucose
hepatomegaly of non-alcoholic fatty liver disease, due to impairment of glycogenolysis causing glycogen accumulation in the liver
in GSD Ib, increased infection risk, due to neutropenia and neutrophil dysfunctionAffected people commonly present with secondary clinical manifestations, linked to one or more of the primary clinical manifestations:

High levels of uric acid in the blood and attendant risk of gout or kidney damage, caused by low serum insulin levels in prolonged hypoglycemia
High levels of lactic acid in the blood, in extreme cases leading to lactic acidosis, caused by prolonged hypoglycemia
hepatic adenomas developing in adulthood and attendant risk of anemia, suspected to be caused by blood glucose dysregulation in the presence of non-alcoholic fatty liver disease
in GSD Ib, inflammatory bowel disease and attendant risk of anemia, caused by neutrophil dysfunction and exacerbated by the increased carbohydrate intake required to prevent hypoglycemiaIn addition, there are several clinical manifestations that often result from the treatment of the primary clinical manifestations:

pancreatic hypertrophy, due to increased carbohydrate intake causing frequent engagement of the insulin response
in GSD Ib, splenomegaly, due to the long-term use of filgrastim to treat neutropenia causing sequestration of blood factors in the spleen
in GSD Ib, an abnormally low number of platelets in the blood may occur, due to long-term use of filgrastim causing sequestration of platelets in the spleen
in GSD Ib, anemia, due to long-term use of filgrastim causing sequestration of hemoglobin in the spleen, potentially exacerbated by uncontrolled inflammatory bowel disease

Hypoglycemia
Low blood sugar (hypoglycemia) is the primary clinical symptom common to both GSD Ia and GSD Ib and most often prompts initial diagnosis of the disease.
Consequences of hyperuricemia among GSD I patients include the development of kidney stones and the accumulation of uric acid crystals in joints, leading to kidney disease and gout, respectively. Hyperlipidemia and plasma effects
Elevated triglycerides in GSD I result from low serum insulin in patients with frequent prolonged hypoglycemia. It may also be caused by intracellular accumulation of glucose-6-phosphate with secondary shunting to pyruvate, which is converted into Acetyl-CoA, which is transported to the cytosol where the synthesis of fatty acids and cholesterol occurs. Triglycerides above the 3.4 mmol/L (300 mg/dL) range may produce visible lipemia, and even a mild pseudohyponatremia due to a reduced aqueous fraction of the blood plasma. In GSD I, cholesterol is typically only mildly elevated compared to other lipids. Hepatomegaly
Impairment in the livers ability to perform gluconeogenesis leads to clinically apparent hepatomegaly. Without this process, the body is unable to liberate glycogen from the liver and convert it into blood glucose, leading to an accumulation of stored glycogen in the liver. Hepatomegaly from the accumulation of stored glycogen in the liver is considered a form of non-alcoholic fatty liver disease. GSD I patients present with a degree of hepatomegaly throughout life, but severity often relates to the consumption of excess dietary carbohydrate. Reductions in the mass of the liver are possible, since most patients retain residual hepatic function that allows for the liberation of stored glycogen at a limited rate. GSD I patients often present with hepatomegaly from the time of birth.