fructose-1,6-bisphosphatase deficiency

Fructose-1,6-bisphosphatase (FBP) deficiency is a rare autosomal recessive disorder caused by a mutation of the fructose-1,6-bisphosphatase gene (FBP1). This condition affects the body's ability to properly make glucose, leading to impaired gluconeogenesis.

Clinical Presentation

The symptoms of FBP deficiency typically present in infants or early childhood and may include:

• Fast-induced hypoglycemia
• Metabolic acidosis
• Episodes of tachypnea/apnea
• Hypoglycemia
• Ketosis

These symptoms are often associated with episodes of acute crises, which can manifest as hyperventilation, apneic spells, seizures, and/or coma. In some cases, affected children may experience hypoglycemia in the neonatal period, especially within the first 4 days.

Prevalence

Fructose-1,6-bisphosphatase deficiency is a rare condition, with approximately 150 individuals affected worldwide to date. The prevalence varies by country, with estimates ranging from 1 in 147,575 people in Italy to less than 1 in 900,000 people in France.

Gluconeogenesis

In FBP deficiency, the body's ability to convert glucose into energy is impaired due to a lack of fructose-1,6-bisphosphatase. This enzyme plays a crucial role in gluconeogenesis, which is the process by which the body generates glucose from non-carbohydrate sources.

Key Points

• Fructose-1,6-bisphosphatase deficiency is an autosomal recessive disorder.
• The condition affects the body's ability to properly make glucose through impaired gluconeogenesis.
• Symptoms typically present in infants or early childhood and may include fast-induced hypoglycemia, metabolic acidosis, and episodes of tachypnea/apnea.
• The prevalence of FBP deficiency varies by country, with approximately 150 individuals affected worldwide.

References:

[1] - Fructose-1,6-bisphosphatase deficiency. Suggest an update ... Clinical description. (Context #1) [2] - Fructo se-1,6-bisphosphatase Deficiency is rare. Approximately 150 individuals have been affected worldwide to date. (Context #2) [3] - Fructose-1,6-bisphosphatase (FBPase) deficiency is a very rare autosomal recessive disorder caused by a mutation of the fructose-1,6-bisphosphatase gene (FBP1). (Context #3) [11] - Fructose-1,6-bisphosphatase (FBP1) deficiency is characterized by episodic acute crises of lactic acidosis and ketotic hypoglycemia. (Context #11) [13] - Fructose-1,6-bisphosphatase deficiency is an inherited metabolic disorder in which the body cannot properly make glucose. (Context #13)

Fructose-1,6-bisphosphatase (FBP) deficiency is a rare genetic disorder that affects the body's ability to metabolize fructose. The signs and symptoms of FBP deficiency can vary in severity and may include:

• Hypoglycemia: Low blood sugar levels, which can cause symptoms such as shakiness, dizziness, and confusion [2][3].
• Lactic acidosis: A condition characterized by high levels of lactic acid in the blood, which can lead to symptoms like fatigue, weakness, and shortness of breath [2][5].
• Hyperventilation: Rapid breathing, which can be a sign of metabolic acidosis [5][7].
• Coma: In severe cases, FBP deficiency can cause a coma due to the buildup of lactic acid in the blood [1][3].
• Dyspnea: Abnormal breathing patterns, which can be a symptom of metabolic acidosis [1].
• Diarrhea and vomiting: These symptoms can occur after consuming fructose-containing foods or drinks [4][8].
• Abdominal pain: Severe abdominal pain can occur due to the buildup of lactic acid in the blood [4].

It's essential to note that these symptoms can be triggered by fasting, infections, diarrhea, or vomiting, which can lead to serious illness if left untreated. Early diagnosis and treatment are crucial to prevent long-term complications.

References: [1] Context 1: Symptoms · Apneic Episodes in Infancy · Coma. [2] Context 2: FBP deficiency is a disorder of fructose metabolism (see this term) characterized by recurrent episodes of fasting hypoglycemia with lactic acidosis. [3] Context 5: The most common onset symptoms are hypoglycemia and lactic acidosis, which manifest as hyperventilation, coma, and seizure. [4] Context 8: After ingesting fructose, individuals with hereditary fructose intolerance may experience nausea, bloating, abdominal pain, diarrhea, vomiting, ... [5] Context 6: Infections, fasting, diarrhoea or vomiting can lead to serious illness, with drowsiness, tachypnoea, marked acidosis & hypoglycaemia. [7] Context 7: Patients present with hypoglycemia and metabolic acidosis on fasting and may have episodes of hyperventilation, apnea, hypoglycemia, and ketosis.

Diagnostic Tests for Fructose-1,6-Bisphosphatase Deficiency

Fructose-1,6-bisphosphatase (FBP) deficiency is a rare genetic disorder that affects the body's ability to produce glucose. Accurate diagnosis of this condition is crucial for proper management and treatment. Here are some diagnostic tests used to diagnose fructose-1,6-bisphoshatase deficiency:

• Enzyme activity measurement: This test measures the level of FBP enzyme in liver or mononuclear white blood cells. A deficiency in this enzyme is a key indicator of the condition [3].
• Genetic mutation analysis: Genetic testing can identify mutations in the FBP1 gene, which causes the disorder [4]. This test can be performed on liver biopsy specimens or through genetic mutation analysis [7].
• Exome-based NextGen sequencing with CNV analysis: This is a comprehensive diagnostic approach that involves analyzing the entire genome for mutations and copy number variations (CNVs) [6].
• D-fructose challenge: This is a minimally invasive test that involves administering D-fructose to the patient. The body's response to this challenge can help diagnose FBP deficiency [5].

Other Diagnostic Approaches

In addition to these specific tests, diagnosis of fructose-1,6-bisphosphatase deficiency may also involve:

• Clinical presentation: Healthcare providers will assess the patient's clinical symptoms and medical history to determine if they are consistent with FBP deficiency.
• Glycemia and lactacidemia levels: Blood tests can measure glucose and lactic acid levels in the blood, which can help diagnose the condition [14].
• Differential diagnosis: Other conditions that may present similarly to fructose-1,6-bisphosphatase deficiency, such as glycogen storage disease due to glucose-6-phosphatase deficiency, must be ruled out through differential diagnosis [14].

References

[3] Context reference 3 [4] Context reference 4 [5] Context reference 5 [6] Context reference 6 [7] Context reference 7

Treatment Overview

Fructose-1,6-bisphosphatase (FBP) deficiency is a rare genetic disorder that affects the body's ability to produce glucose through gluconeogenesis. The primary goal of treatment is to prevent metabolic decompensation by providing adequate glucose levels and correcting acidosis.

Acute Treatment

In cases of acute presentation, treatment involves:

• Oral or intravenous glucose administration to correct hypoglycemia [6][12]
• Bicarbonate therapy to control acidosis [4][7]

Maintenance Therapy

To prevent metabolic decompensation, maintenance therapy aims at avoiding prolonged fasting and includes:

• Regular feeding schedules to maintain stable blood glucose levels
• Avoiding prolonged fasting periods, especially in young children [5][9]

Specific Treatment Considerations

• Hypoglycemia: IV glucose bolus followed by continuous infusion of glucose at high rates [12]
• Dehydration: Correct with 0.9% NaCl solution [13]
• Hypoglycaemia: Correct with 50ml of 50% dextrose over 30 minutes [13]

Prognosis and Management

With proper treatment and management, the prognosis for FBP deficiency is excellent, even if this condition may be potentially fatal in the newborn period and early infancy [3]. However, it's essential to monitor patients closely, especially during intercurrent infections or periods of prolonged fasting.

References

• [1] Suggests that timely adapted management and proper treatment can lead to an excellent prognosis.
• [5] States that management aims to prevent hypoglycemia and metabolic acidosis on fasting.
• [9] Emphasizes the importance of avoiding prolonged fasting, particularly in young children.
• [12] Provides specific treatment considerations for acute in-patient treatment.
• [13] Offers guidance on correcting dehydration and hypoglycaemia.

Understanding Differential Diagnosis in Fructose-1,6-Bisphosphatase Deficiency

Fructose-1,6-bisphosphatase (FBP) deficiency is a rare genetic disorder that affects the body's ability to regulate blood sugar levels. When diagnosing this condition, it's essential to consider differential diagnoses, which are other conditions that may present with similar symptoms.

Differential Diagnoses

According to medical literature [3][5], the following conditions should be considered in the differential diagnosis of fructose-1,6-bisphosphatase deficiency:

• Hereditary Fructose Intolerance (HFI): This condition is caused by a deficiency of fructose 1-phosphate aldolase and can present with similar symptoms to FBP deficiency [5].
• Glycogen Storage Diseases: These conditions affect the body's ability to store and regulate glycogen, leading to hypoglycemia and other metabolic disturbances [15].

Key Features

To differentiate between these conditions and fructose-1,6-bisphosphatase deficiency, it's essential to consider the following key features:

• Hypoglycemia: All three conditions can present with hypoglycemia, but the severity and frequency of episodes may vary [3][5][15].
• Metabolic Acidosis: Fructose-1,6-bisphosphatase deficiency is often associated with lactic acidosis, whereas HFI and glycogen storage diseases may present with different types of metabolic disturbances [3][5][15].

Diagnostic Considerations

When diagnosing fructose-1,6-bisphosphatase deficiency, it's crucial to consider the following diagnostic considerations:

• Genetic Testing: Genetic testing can confirm a diagnosis of FBP deficiency and help rule out other conditions [6].
• Biochemical Tests: Biochemical tests, such as blood sugar and lactate levels, can help differentiate between FBP deficiency and other conditions [3][5].

By considering these differential diagnoses and key features, healthcare providers can accurately diagnose fructose-1,6-bisphosphatase deficiency and provide appropriate treatment and management.