Essential fructosuria, caused by a deficiency of the enzyme hepatic fructokinase, is a clinically

benign Malignancy () is the tendency of a medical condition to become progressively worse; the term is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malig ...

condition characterized by the incomplete metabolism of

fructose Fructose (), or fruit sugar, is a Ketose, ketonic monosaccharide, simple sugar found in many plants, where it is often bonded to glucose to form the disaccharide sucrose. It is one of the three dietary monosaccharides, along with glucose and gal ...

in the liver, leading to its excretion in urine. Fructokinase (sometimes called ketohexokinase) is the first enzyme involved in the degradation of fructose to fructose-1-phosphate in the liver. This defective degradation does not cause any clinical symptoms, fructose is either excreted unchanged in the urine or metabolized to fructose-6-phosphate by alternate pathways in the body, most commonly by

hexokinase A hexokinase is an enzyme that irreversibly phosphorylates hexoses (six-carbon sugars), forming hexose phosphate. In most organisms, glucose is the most important substrate for hexokinases, and glucose-6-phosphate is the most important p ...

in adipose tissue and muscle.

Signs and symptoms

Cause

Essential fructosuria is a genetic condition that is inherited in an

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

manner. Mutations in the ''KHK'' gene, located on chromosome 2p23.3-23.2 are responsible. The incidence of essential fructosuria has been estimated at 1:130,000. The actual incidence is likely higher, because those affected are asymptomatic.

Diagnosis

A diagnosis of essential fructosuria is typically made after a positive routine test for reducing sugars in the urine. An additional test with glucose oxidase must also be carried out (with a negative result indicating essential fructosuria) as a positive test for reducing sugars is most often a result of glucosuria secondary to

diabetes mellitus Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained hyperglycemia, high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or th ...

. The excretion of fructose in the urine is not constant, it depends largely on dietary intake.

Treatment

No treatment is indicated for essential fructosuria, while the degree of fructosuria depends on the dietary fructose intake, it does not have any clinical manifestations. The amount of fructose routinely lost in urine is quite small. Other errors in fructose metabolism have greater clinical significance. Hereditary fructose intolerance, or the presence of fructose in the blood (fructosemia), is caused by a deficiency of aldolase B, the second enzyme involved in the metabolism of fructose. This enzyme deficiency results in an accumulation of fructose-1-phosphate, which inhibits the production of

glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...

and results in diminished regeneration of

adenosine triphosphate Adenosine triphosphate (ATP) is a nucleoside triphosphate that provides energy to drive and support many processes in living cell (biology), cells, such as muscle contraction, nerve impulse propagation, and chemical synthesis. Found in all known ...

. Clinically, patients with hereditary fructose intolerance are much more severely affected than those with essential fructosuria, with elevated

uric acid Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the Chemical formula, formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the meta ...

, growth abnormalities and can result in coma if untreated.

References

External links

{{Carbohydrate metabolic pathology Autosomal recessive disorders Inborn errors of carbohydrate metabolism