Fructosuria (hepatic fructokinase disorder)

Obesity

Parkinson's disease
Summary

Fructosuria is a rare autosomal recessive disorder with no known clinical manifestations, in which

fructose is excreted in the urine. Fructosuria is inherited as an autosomal recessive trait caused by

mutations in the hepatic fructokinase gene (KHK) on chromosome 19p13.2-p13.1. A number of

mutations have been described so far; however, the most common mutation associated with this condition

being pSer369Cys mutation which has been reported primarily in Italian patients affected by fructosuria.

The diagnosis of fructosuria is based on high quantitative levels of urinary fructose detected in routine or

specialized laboratory testing after an overnight fast and after a test meal containing fructose-containing

foods such as fruit juices or other soft drinks.

Fructosuria, or hepatic fructokinase disorder, is due to a mutation in the gene encoding the enzyme

fructokinase. This enzyme catalyzes the conversion of fructose-1-phosphate to fructose 6-phosphate and

glucose 1-phosphate.[5] The most common effects are asymptomatic hyperuricemia and hyperuricosuria.

[7]

The clinical spectrum of fructosuria ranges from isolated elevations in serum uric acid levels to severe

metabolic disorders involving multiple organs and tissues (including joint pain) that can be life

threatening if left untreated.[8],[9]

The prevalence of fructosuria is rare but has been reported worldwide, with an incidence rate of 1 in 50

000 births in the Nordic countries.

fructokinase, which causes high urinary excretion of fructose. The most common effects are

asymptomatic hyperuricemia and hyperuricosuria.

Define disease/metabolic disorder & its prevalence / epidemiology

Fructosuria, or hepatic fructokinase disorder, is due to a mutation in the gene encoding the enzyme
fructokinase, which causes high urinary excretion of fructose. The most common effects are
asymptomatic hyperuricemia and hyperuricosuria.

Fructosuria is a rare autosomal recessive disorder with no known clinical manifestations, in which
fructose is excreted in the urine.

Fructosuria has been reported in several populations around the world, including Canada, Italy, Spain,
and Vietnam. One study has shown that around 1% of the population in Italy may carry one of the two
most common variants associated with fructosuria; however more detailed studies on prevalence must be
conducted before any solid conclusions can be reached on the prevalence of fructosuria.

Fructosuria has been reported in several populations around the world, including Canada, Italy, Spain,
and Vietnam. One study has shown that around 1% of the population in Italy may carry one of the two
most common variants associated with fructosuria; however more detailed studies on prevalence must be
conducted before any solid conclusions can be reached on the prevalence of fructosuria.

✘ Prevalence - Fructosuria is rare but has been reported worldwide, with an incidence rate of 1 in 50 000
births in the Nordic countries.

Fructosuria is a rare autosomal recessive disorder with no known clinical manifestations, in which
fructose is excreted in the urine. It has been reported to occur in less than 1/10th of 1% of the population
and is caused by mutations in hepatic fructokinase (HFK). Fructose may be removed from circulation
through conversion to glycogen or lactate by HFK. When this enzyme is absent or deficient, fructose
accumulates in the blood stream and eventually crosses into urine where it can be detected by dipstick
testing.*

Fructosuria has been reported in several populations around the world, including Canada, Italy, Spain,
and Vietnam. One study has shown that around 1% of the population in Italy may carry one of the two
most common variants associated with fructosuria; however more detailed studies on prevalence must be
conducted before any solid conclusions can be reached on the prevalence of fructosuria.

Fructosuria has been reported in several populations around the world, including Canada, Italy, Spain and
Vietnam. One study has shown that around 1% of the population in Italy may carry one of the two most
common variants associated with fructosuria; however more detailed studies on prevalence must be
conducted before any solid conclusions can be reached on the prevalence of fructosuria.

In addition to being present at birth, there are no other known risk factors for this condition which
indicates that it is likely inherited as an autosomal recessive trait (i.e., both parents must carry a copy of a
mutated gene).

Clinical Characteristics/description

Clinically, patients with fructosuria have been reported to be asymptomatic and develop normally, and no
formal studies on other conditions or requirements for treatment have been made.

✓ Clinical Characteristics/description - Fructosuria usually has no clinical effect other than mild
hyperuricosuria (high levels of uric acid in urine), and hence no treatment is required. Less commonly,
patients have recurrent cystitis or kidney stones. Some patients undergo evaluation for hemolytic anemia
as a result of very low or no red blood cell production.

Fructosuria is a rare inherited metabolic disorder that affects about 1 in 100,000 people. It results from an
enzyme deficiency that prevents the body from breaking down fructose (a type of sugar). This can lead to
serious complications if left untreated; however, most cases are mild and require no treatment.

Fructosuria usually has no clinical effect other than mild hyperuricosuria (high levels of uric acid in
urine), and hence no treatment is required. Less commonly, patients have recurrent cystitis or kidney
stones. Some patients undergo evaluation for hemolytic anemia as a result of very low or no red blood
cell production.

Fructosuria is an autosomal recessive disorder that results from a deficiency of hepatic fructokinase,
which results in the inability to metabolize fructose normally. This causes excess quantities of fructose to
be excreted in the urine and ultimately leads to the accumulation of large amounts of uric acid in the
blood. Patients with fructosuria are able to metabolize glucose normally, but at a reduced rate compared
to individuals without this condition.

Causes

Causes - Deficiency of fructokinase results in increased fructose concentrations in blood, higher levels of
uric acid in the blood and urine , and accelerated hepatic glycogen synthesis, but it has little or no effect
on the homeostasis of other carbohydrates.

Deficiency of fructokinase results in increased fructose concentrations in blood, higher levels of uric acid
in the blood and urine, and accelerated hepatic glycogen synthesis. It has little or no effect on the
homeostasis of other carbohydrates.

Pathophysiology & Molecular Pathogenesis along figures

Diagnosis & Testing (Biochemical testing, Molecular testing)

The diagnosis of fructosuria is based on high quantitative levels of urinary fructose detected in routine or
specialized laboratory testing after an overnight fast and after a test meal containing fructose-containing
foods such as fruit juices or other soft drinks.

The exact mode of inheritance is not known. It is thought to be autosomal recessive, because affected
individuals usually have consanguineous parents. However, it has been reported that some non-
consanguineous couples have produced affected offspring.

One study reported a higher prevalence of fructosuria in children born to diabetic mothers than those born
to non-diabetic mothers; this suggests that maternal diabetes may play an important role in the
development of fructosuria (1).
Genetic Counseling

Genetic related (Allelic) disorders & Mode of inheritance ✓Mechanism / Biochemical manifestation
along diagram

Genetic related (Allelic) disorders & Mode of inheritance - Fructosuria is inherited as an autosomal
recessive trait caused by mutations in the hepatic fructokinase gene (KHK-F) on chromosome 19p13.2-
p13.1. A number of mutations have been described .

It is inherited as an autosomal recessive trait and is caused by mutations in the hepatic fructokinase
(KHK) gene, with the most common mutation associated with this condition being the p.Ser369Cys
mutation. Patients with fructosuria are able to metabolize fructose normally, but at a reduced rate of
metabolism compared to individuals without this condition.

Fructosuria is inherited as an autosomal recessive trait and is caused by mutations in the hepatic
fructokinase (KHK) gene, with the most common mutation associated with this condition being the
p.Ser369Cys mutation.

Patients with fructosuria are able to metabolize fructose normally, but at a reduced rate of metabolism
compared to individuals without this condition.

Management

Conclusion

The diagnosis of fructosuria is based on high quantitative levels of urinary fructose detected in routine or
specialized laboratory testing after an overnight fast and after a test meal containing fructose-containing
foods such as fruit juices or other soft drinks.

References/literature cited (References must properly mentioned in text)