Fructose-1,6-bisphosphatase deficiency (FBP1D) is a rare inherited metabolic condition that impairs the body’s ability to create glucose. This disorder disrupts an energy-producing process, leaving an individual vulnerable during periods without food. The condition typically becomes apparent in early infancy and requires lifelong management to prevent serious health complications.
Genetic and Metabolic Causes
The human body maintains energy levels during fasting through a process called gluconeogenesis, which involves creating glucose from non-carbohydrate sources. The enzyme fructose-1,6-bisphosphatase performs a necessary step in this pathway. Without this enzyme, the pathway is blocked, and the body cannot produce the glucose it needs when dietary sources are unavailable.
Fructose-1,6-bisphosphatase deficiency is caused by mutations in the FBP1 gene, which contains the instructions for building the fructose-1,6-bisphosphatase enzyme. When mutations alter these instructions, the resulting enzyme is either non-functional or produced in insufficient quantities. This genetic defect is the cause of the metabolic problems seen in the disorder.
The condition is inherited in an autosomal recessive pattern. This means a child must inherit one copy of the mutated FBP1 gene from each parent to be affected. The parents, who each have one normal and one mutated copy, are considered carriers and do not exhibit symptoms of the disorder.
Recognizing the Symptoms
The inability to produce glucose during fasting leads to the symptoms of FBP1D. These issues first appear in infants between three and four months of age, when babies begin to sleep for longer stretches overnight. This extended period without feeding triggers a metabolic crisis characterized by dangerously low blood sugar, a condition called hypoglycemia.
During these episodes, the body attempts to compensate for the lack of glucose, leading to a buildup of other substances in the blood. This results in lactic acidosis, an accumulation of lactic acid that makes the blood too acidic. This is accompanied by ketosis, where the body produces high levels of ketones as an alternative fuel source.
These metabolic disturbances manifest as observable signs. Parents may notice their infant becoming lethargic, irritable, or difficult to feed. Other symptoms include rapid breathing (hyperventilation) and hypotonia, or a “floppy” muscle tone. A severe metabolic crisis can lead to apnea (pauses in breathing), seizures, and coma.
These episodes are frequently set off by common childhood illnesses, such as a fever or a stomach virus. These events increase the body’s energy demands or reduce food intake, triggering a crisis.
The Diagnostic Journey
Diagnosing FBP1D often begins when a child is brought to the hospital during their first metabolic crisis. Initial laboratory tests on blood and urine samples provide the first clues. These tests reveal severe hypoglycemia along with high levels of lactate and ketones. Urine tests may also show abnormal patterns of organic acids.
Confirmation of the diagnosis requires more specialized testing. Historically, this involved a liver biopsy to directly measure the activity of the fructose-1,6-bisphosphatase enzyme. A significant reduction or absence of enzyme activity would confirm the diagnosis. This invasive procedure is now less common.
Today, molecular genetic testing is the standard method for a definitive diagnosis. By sequencing the FBP1 gene, clinicians can identify the specific disease-causing mutations, which avoids a liver biopsy. FBP1D is not consistently included in standard newborn screening panels, so the diagnosis is often made only after a child becomes symptomatic.
Long-Term Management and Diet
The foundation of managing FBP1D is the prevention of hypoglycemia. This is achieved through careful dietary planning aimed at avoiding any situation that would require the body to make its own glucose. The primary rule is the strict avoidance of fasting for prolonged periods.
Dietary management involves eliminating specific sugars that feed into the blocked metabolic pathway. Individuals must avoid all sources of the following:
- Fructose, which is found naturally in fruits and honey.
- Sucrose, or common table sugar, which is composed of glucose and fructose.
- Sorbitol, an artificial sweetener that the body converts to fructose.
To ensure a constant supply of energy, the diet relies on frequent meals and snacks rich in complex carbohydrates. These foods are broken down slowly, providing a steady release of glucose. For infants and young children, this often includes uncooked cornstarch, which acts as a slow-release form of glucose overnight to maintain stable blood sugar levels.
Families must also have a clear emergency protocol for times of illness, which can trigger a metabolic crisis. This plan involves a letter for emergency medical personnel that explains the condition and the need for intravenous glucose. Promptly treating any illness and providing a source of glucose can prevent severe complications. With diligent dietary adherence and management, individuals with FBP1D can lead a normal life.