Essential fructosuria was first described independently by Czapek and Zimmer in a man who also suffered from diabetes mellitus. Laron counted 50 published cases, of which 18 were in Jews. The enzyme deficiency was demonstrated in liver by Schapira et al. Khachadurian described nonalimentary fructosuria in an month-old Arab boy who suffered from sickle-cell thalassemia.
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Properties of normal and mutant recombinant human ketohexokinases and implications for the pathogenesis of essential fructosuria. Alternative splicing of the ketohexokinase fructokinase gene generates a "central" predominantly hepatic isoform ketohexokinase-C and a more widely distributed ketohexokinase-A.
Only the abundant hepatic isoform is known to possess activity, and no function is defined for the lower levels of ketohexokinase-A in peripheral tissues. Hepatic ketohexokinase deficiency causes the benign disorder essential fructosuria.
The molecular basis of this has been defined in one family compound heterozygosity for mutations Gly40Arg and Ala43Thr. Here we show that both ketohexokinase isoforms are indeed active. Ketohexokinase-A has much poorer substrate affinity than ketohexokinase-C for fructose but is considerably more thermostable.
The Gly40Arg mutation seems null, rendering both ketohexokinase-A and ketohexokinase-C inactive and largely insoluble. The Ala43Thr mutant retains activity, but this mutation decreases the thermal stability of both ketohexokinase-A and ketohexokinase-C.
At physiologic temperature, this results in significant loss of ketohexokinase-C activity but not of ketohexokinase-A. Affected individuals who carry both mutations therefore probably have a selective deficiency of hepatic ketohexokinase, with peripheral ketohexokinase-A being preserved.
These findings raise the possibility that ketohexokinase-A serves an unknown physiologic function that remains intact in essential fructosuria. Further mutation analysis in this rare disorder could illuminate the question of whether ketohexokinase-A activity is, unlike that of ketohexokinase-C, physiologically indispensable.
Cause[ edit ] Essential fructosuria is a genetic condition that is inherited in an autosomal recessive manner. The incidence of essential fructosuria has been estimated at , Diagnosis[ edit ] 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. The excretion of fructose in the urine is not constant, it depends largely on dietary intake. 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.