Fructosuria, Essential

A number sign (#) is used with this entry because of evidence that essential fructosuria is caused by compound heterozygous mutation in the KHK gene (614058) on chromosome 2p23.

Description

Essential fructosuria is a benign, asymptomatic defect of intermediary metabolism characterized by the intermittent appearance of fructose in the urine (summary by Bonthron et al., 1994).

Clinical Features

In individuals with essential fructosuria, ingestion of dietary fructose, sucrose, or sorbitol is followed by an abnormally large and persistent rise in blood fructose concentration and by excretion of 10 to 20% of the ingested load in the urine (Gitzelmann et al., 1989).

Essential fructosuria was first described independently by Czapek (1876) and Zimmer (1876) in a man who also suffered from diabetes mellitus. Laron (1961) counted 50 published cases, of which 18 were in Jews. The enzyme deficiency was demonstrated in liver by Schapira et al. (1961).

Khachadurian (1963) described nonalimentary fructosuria in an 18-month-old Arab boy who suffered from sickle-cell thalassemia. The fructose tolerance test was normal and fructosuria persisted after fructose was entirely excluded from the diet, but had decreased markedly when the patient was seen 2 years later. Both the spleen and the liver were enlarged. The patient's parents were first cousins. Urine samples from both parents were negative for a reducing substance. Urine samples from the brother and 2 sisters showed intermittent fructosuria. Small amounts of fructose occur in the urine of normal individuals ingesting a regular diet but amounts sufficient to give a positive test for reducing sugar in the routine examination occur only in essential fructosuria, familial fructose intolerance, and advanced liver disease.

Using (31)P magnetic resonance spectroscopy to measure changes in liver metabolite concentrations in adults with fructosuria, Boesiger et al. (1994) found that concentrations of fructose-1-phosphate, ATP, and inorganic phosphate remained unchanged, confirming that fructokinase was indeed inactive.

Inheritance

Lasker (1941) documented autosomal recessive inheritance of essential fructosuria.

Molecular Genetics

In a well-characterized family in which 3 of 8 sibs had fructosuria (Steinmann and Gitzelmann, 1981; Gitzelmann et al., 1989; Boesiger et al., 1994), Bonthron et al. (1994) found that all affected individuals were compound heterozygous for 2 mutations in the KHK gene: gly40-to-arg (614058.0001) and ala43-to-thr (614058.0002). Both mutations resulted from a G-to-A transition, and each altered the same conserved region of the KHK protein. Neither mutation was seen in a sample of 52 unrelated control individuals.