Early research into<unk>  identified numerous clinical manifestations falsely thought to be primary features of the genetic disorder. However, continuing research has revealed that these clinical features are the consequences of only one (in<unk> a) or two (in<unk> b) fundamental abnormalities: * impairment in the liver's ability to convert stored glycogen into glucose through glycogenolysis * in<unk> b, impairment of the neutrophil's ability to take up glucose, resulting in neutrophil dysfunction and neutropenia These fundamental abnormalities give rise to a small number of primary clinical manifestations, which are the features considered in diagnosis of<unk> : * Low blood sugar (hypoglycemia), due to impairment of glycogen breakdown (glycogenolysis) causing insufficient fasting blood glucose * hepatomegaly of non-alcoholic fatty liver<unk> , due to impairment of glycogenolysis causing glycogen accumulation in the liver * in<unk> b, increased infection risk, due to neutropenia and neutrophil dysfunction Affected 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<unk>  * in<unk> b, inflammatory bowel<unk>  and attendant risk of anemia, caused by neutrophil dysfunction and exacerbated by the increased carbohydrate intake required to prevent hypoglycemia In 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<unk> b, splenomegaly, due to the long-term use of filgrastim to treat neutropenia causing sequestration of blood factors in the spleen * in<unk> b, 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<unk> b, anemia, due to long-term use of filgrastim causing sequestration of hemoglobin in the spleen, potentially exacerbated by uncontrolled inflammatory bowel<unk>  Hypoglycemia Low blood sugar (hypoglycemia) is the primary clinical symptom common to both<unk> a and<unk> b and most often prompts initial diagnosis of the<unk> . During fetal development in utero, maternal glucose transferred across the placenta prevents hypoglycemia. However, after birth, the inability to maintain blood glucose from stored glycogen in the liver causes measurable hypoglycemia in no more than 1–2 hours after feedings. Without proper dietary treatment after birth, prolonged hypoglycemia often leads to sudden lactic acidosis that can induce primary respiratory distress in the newborn period, as well as ketoacidosis. Neurological manifestations of hypoglycemia are less severe in<unk>  than in other instances. Rather than acute hypoglycemia,<unk>  patients experience persistent mild hypoglycemia. The diminished likelihood of neurological manifestations is due to the habituation of the brain to mild hypoglycemia. Given the reduced blood glucose level, the brain adapts to using alternative fuels like lactate. These gradual metabolic adaptations during infancy make severe symptoms like unconsciousness or seizure uncommon before diagnosis. In the early weeks of life, undiagnosed infants with<unk>  tolerate persistent hypoglycemia and compensated lactic acidosis between feedings without symptoms. Without consistent carbohydrate feeding, infant blood glucose levels typically measure between 25 and 50 mg/dL (1.4 to 2.8 mmol/L). After weeks to months without treatment with consistent oral carbohydrates, infants will progress to show clear symptoms of hypoglycemia and lactic acidosis. Infants may present with paleness, clamminess, irritability, respiratory distress, and an inability to sleep through the night even in the second year of life. Developmental delay is not an intrinsic effect of<unk> , but is common if the diagnosis is not made in early infancy.
Glycogen storage disease type I
Glycogen storage disease type 0
Glycogen storage disease type V
Glycogen storage disease type VI
Essential fructosuria
Inborn errors of carbohydrate metabolism
Aspartylglucosaminuria
Familial dysbetalipoproteinemia