Information about Fructose Bisphosphatase Deficiency

Classification & external resources

Fructose 1,6-bisphosphate
ICD-10	E74.1
OMIM	229700
DiseasesDB	5012
eMedicine	ped/806
MeSH	D015319

In Fructose bisphosphatase deficiency, there is not enough fructose bisphosphatase for gluconeogenesis to occur correctly. Glycolysis (the break-down of glucose) will still work, as it does not use this enzyme.

Presentation

Without effective gluconeogenesis (GNG), hypoglycaemia will set in after about 12 hours. This is the time when liver glycogen stores have been exhausted, and the body has to rely on GNG. When given a dose of glucagon (which would normally increase blood glucose) nothing will happen, as stores are depleted and GNG doesn't work. (In fact, the patient would already have high glucagon levels.)

There is no problem with the metabolism of glucose or galactose, but fructose and glycerol cannot be used as fuels. If fructose or glycerol are given, there will be a build up of phosphorylated three-carbon sugars. This leads to phosphate depletion within the cells, and also in the blood. Without phosphate, ATP cannot be made, and many cell processes cannot occur.

High levels of glucagon will tend to release fatty acids from adipose tissue, and this will combine with glycerol that cannot be used in the liver, to make triacylglycerides causing a fatty liver.

As three carbon molecules cannot be used to make glucose, the will instead be made into pyruvate and lactate. These acids cause a drop in the pH of the blood (a metabolic acidosis). Acetyl CoA (acetyl co-enzyme A) will also build up, leading to the creation of ketone bodies.

Treatment

To treat people with a deficiency of this enzyme, they must avoid needing gluconeogenesis to make glucose. This can be accomplished by not fasting for long periods, and eating high-carbohydrate food. They should avoid fructose containing foods (as well as sucrose which breaks down to fructose).

As with all single-gene metabolic disorders, there is always hope for genetic therapy, inserting a healthy copy of the gene into existing liver cells.

See also

• Fructose
• Gluconeogenesis
• Metabolism

References

• diMauro, Salvatore; Darryl C. De Vivo (October 1998). "Diseases of Carbohydrate, Fatty Acid and Mitochondrial Metabolism", in George J. Siegel et al (ed.): Basic Neurochemistry: Molecular, Cellular and Medical Aspects, 6th Edition, Philadelphia, Pennsylvania: Lippincott Williams and Wilkins. ISBN 0-7817-1745-0. 

•  • [ e] Metabolic pathology (, )
Amino acid	Aromatic (Phenylketonuria, Alkaptonuria, Ochronosis, Tyrosinemia, Albinism, Histidinemia) - Branched chain (Maple syrup urine disease, Propionic acidemia, Methylmalonic acidemia, Isovaleric acidemia, 3-Methylcrotonyl-CoA carboxylase deficiency) - Transport (Cystinuria, Cystinosis, Hartnup disease, Fanconi syndrome) - Sulfur (Homocystinuria, Cystathioninuria) - Urea cycle disorder (N-Acetylglutamate synthase deficiency, Carbamoyl phosphate synthetase I deficiency, Ornithine transcarbamylase deficiency, Citrullinemia, Argininosuccinic aciduria, Hyperammonemia) - Glutaric acidemia type 1 - Sarcosinemia
Carbohydrate	Lactose intolerance - Glycogen storage disease (type I, type II, type III, type IV, type V, type VI, type VII) - fructose metabolism (Fructose intolerance, Fructose bisphosphatase deficiency, Essential fructosuria) - galactose metabolism (Galactosemia, Galactose-1-phosphate uridylyltransferase galactosemia, Galactokinase deficiency) - other intestinal carbohydrate absorption (Glucose-galactose malabsorption, Sucrose intolerance) - pyruvate metabolism and gluconeogenesis (PCD, PDHA) - Pentosuria - Renal glycosuria
Lipid storage	Sphingolipidoses/Gangliosidoses: GM2 gangliosidoses (Sandhoff disease, Tay-Sachs disease) - GM1 gangliosidoses - Mucolipidosis type IV - Gaucher's disease - Niemann-Pick disease - Farber disease - Fabry's disease - Metachromatic leukodystrophy - Krabbe disease Neuronal ceroid lipofuscinosis (Batten disease) - Cerebrotendineous xanthomatosis - Cholesteryl ester storage disease (Wolman disease)
Other lipid	Lipoprotein/lipidemias: Hyperlipidemia - Hypercholesterolemia - Familial hypercholesterolemia - Xanthoma - Combined hyperlipidemia - Lecithin cholesterol acyltransferase deficiency - Tangier disease - Abetalipoproteinemia Fatty acid: Adrenoleukodystrophy - Carnitine (Primary, I, II)
Mineral	Cu Wilson's disease/Menkes disease - Fe Haemochromatosis - Zn Acrodermatitis enteropathica - PO43− Hypophosphatemia/Hypophosphatasia - Mg2+ Hypermagnesemia/Hypomagnesemia - Ca2+ Hypercalcaemia/Hypocalcaemia/Disorders of calcium metabolism
Fluid, electrolyte and acid-base balance	Electrolyte disturbance - Na+ Hypernatremia/Hyponatremia - Acidosis (Metabolic, Respiratory, Lactic) - Alkalosis (Metabolic, Respiratory) - Mixed disorder of acid-base balance - H2O Dehydration/Hypervolemia - K+ Hypokalemia/Hyperkalemia - Cl− Hyperchloremia/Hypochloremia
Purine and pyrimidine	Hyperuricemia - Lesch-Nyhan syndrome - Xanthinuria
Porphyrin	Acute intermittent, Gunther's, Cutanea tarda, Erythropoietic, Hepatoerythropoietic, Hereditary copro-, Variegate
Bilirubin	Unconjugated (Gilbert's syndrome, Crigler-Najjar syndrome) - Conjugated (Dubin-Johnson syndrome, Rotor syndrome)
Glycosaminoglycan	Mucopolysaccharidosis - 1:Hurler/Hunter - 3:Sanfilippo - 4:Morquio - 6:Maroteaux-Lamy - 7:Sly
Glycoprotein	Mucolipidosis - I-cell disease - Pseudo-Hurler polydystrophy - Aspartylglucosaminuria - Fucosidosis - Alpha-mannosidosis - Sialidosis
Other	Alpha 1-antitrypsin deficiency - Cystic fibrosis - Amyloidosis (Familial Mediterranean fever) - Acatalasia