Fructose-1,6-bisphosphatase deficiency

Fructose-1,6-bisphosphatase (FBPase) deficiency is a rare inherited disorder of gluconeogenesis, the metabolic pathway by which the body produces glucose from non-sugar sources such as amino acids, glycerol, and lactate. It is caused by mutations in the FBP1 gene, which encodes the enzyme fructose-1,6-bisphosphatase. This enzyme plays a critical role in maintaining blood sugar levels during fasting. When the enzyme is deficient, the body cannot adequately produce glucose during periods of fasting or illness, leading to episodes of hypoglycemia (low blood sugar) and lactic acidosis (buildup of lactic acid in the blood). The condition typically presents in infancy or early childhood, often triggered by fasting, febrile illness, or increased physical activity. Key clinical features include episodes of hypoglycemia, lactic acidosis, hyperventilation (Kussmaul breathing), irritability, drowsiness, and in severe cases, seizures and coma. Between episodes, affected individuals are usually completely well. Hepatomegaly (enlarged liver) may be present during acute crises due to fat accumulation in the liver. Some patients may also experience ketosis during metabolic decompensation. There is no cure for FBPase deficiency, but the condition is manageable with appropriate dietary and medical interventions. The cornerstone of treatment is avoidance of prolonged fasting. Patients are advised to eat frequent meals rich in complex carbohydrates and to limit fructose and sucrose intake. During acute episodes, intravenous glucose administration is essential to correct hypoglycemia and suppress lactic acid production. With early diagnosis and careful management, the long-term prognosis is generally favorable, and most individuals can lead normal lives. Metabolic crises tend to become less frequent with age as the body's glycogen stores increase relative to metabolic demands.

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