What are the other Names for this Condition? (Also known as/Synonyms)

• Baker-Winegrad Disease
• Fructose 1,6 Diphosphatase Deficiency Disorder

What is Fructose-1,6-Bisphosphatase Deficiency Disorder? (Definition/Background Information)

• Fructose-1,6-Bisphosphatase Deficiency Disorder is an inherited metabolic disorder in which the body cannot properly make glucose. Glucose is the main type of sugar in the blood and a primary source of energy for the body's cells
• Without treatment, affected people can experience hypoglycemia and metabolic acidosis on fasting, episodes of hyperventilation, suspension of breathing (apnea), and elevated levels of ketones in their blood (ketosis)
• Fructose-1,6-Bisphosphatase Deficiency Disorder is inherited in an autosomal recessive manner. Inherited mutations in the FBP1 gene cause a deficiency of the enzyme fructose-1,6-bisphosphatase. This deficiency, in turn, results in impaired production of glucose
• This disorder can be treated by complete avoidance of fructose and its related sugars, as well as by avoiding prolonged periods of fasting. Typically, having of small amounts of fructose and related sugars may be tolerated in most patients with Fructose-1,6-Bisphosphatase Deficiency Disorder. No other specific medical therapy is generally required

(Source: Fructose-1,6-Bisphosphatase Deficiency Disorder; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Fructose-1,6-Bisphosphatase Deficiency Disorder? (Age and Sex Distribution)

• Fructose-1,6-Bisphosphatase Deficiency Disorder is a rare congenital disorder. The presentation of symptoms may occur at all ages
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Fructose-1,6-Bisphosphatase Deficiency Disorder? (Predisposing Factors)

• A positive family history may be an important risk factor, since Fructose-1,6-Bisphosphatase Deficiency Disorder can be inherited
• Currently, no other risk factors have been clearly identified for this deficiency disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Fructose-1,6-Bisphosphatase Deficiency Disorder? (Etiology)

Fructose-1,6-Bisphosphatase Deficiency Disorder is caused by mutation(s) in the FBP1 gene.

• The FBP1 gene codes for the fructose-1,6- biphosphatase 1 enzyme, and mutation(s) in this gene may cause a deficiency of the enzyme, leading to the disorder
• The recessive mutations in the two copies of FBP1 gene can either be in the same locus or different loci, to result in the deficiency of FBP1 enzyme
• When the mutations are in different loci on copies of the same gene, it is known as a compound heterozygous mutation
• Fructose-1,6-Bisphosphatase Deficiency Disorder is inherited in an autosomal recessive manner

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Fructose-1,6-Bisphosphatase Deficiency Disorder?

The signs and symptoms of Fructose-1,6-Bisphosphatase Deficiency Disorder may include:

• Apnea
• Dyspnea
• Fever
• Generalized hypotonia
• Hepatomegaly
• Hyperventilation
• Increased urinary glycerol
• Irritability
• Ketosis
• Lethargy
• Metabolic acidosis
• Tachycardia

(Source: Fructose-1,6-Bisphosphatase Deficiency Disorder; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Fructose-1,6-Bisphosphatase Deficiency Disorder Diagnosed?

Fructose-1,6-Bisphosphatase Deficiency Disorder is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms 
• Laboratory tests, including:
  • Blood tests for checking glucose and lactic acid levels
  • FBP1 enzyme activity assays in leukocytes
• Imaging studies
• Biopsy studies, if necessary
• Molecular genetic testing to check for or confirm FBP1 gene mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Fructose-1,6-Bisphosphatase Deficiency Disorder?

The complications of Fructose-1,6-Bisphosphatase Deficiency Disorder may include:

• Fainting episodes
• Coma

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Fructose-1,6-Bisphosphatase Deficiency Disorder Treated?

There is no cure for Fructose-1,6-Bisphosphatase Deficiency Disorder, since it is a genetic condition. However, the condition can be efficiently managed by:

• Avoiding fructose and related sugars
• Frequent meals and avoiding fasting longer than 8 hours

How can Fructose-1,6-Bisphosphatase Deficiency Disorder be Prevented?

Currently, Fructose-1,6-Bisphosphatase Deficiency Disorder may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Fructose-1,6-Bisphosphatase Deficiency Disorder? (Outcomes/Resolutions)

• The prognosis of Fructose-1,6-Bisphosphatase Deficiency Disorder is excellent, with an early diagnosis and prompt and continued management of the condition
• However, delay in diagnosis or treatment, specifically in the newborn or infancy phase, can be life-threatening

Additional and Relevant Useful Information for Fructose-1,6-Bisphosphatase Deficiency Disorder:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/