Fructose-1-phosphate aldolase deficiency

Genetic deficiency of fructokinase is benign and often detected incidentally when the urine is checked for glucose with a dipstick. Fructose 1-phosphate aldolase deficiency is a severe disease because of accumulation of fructose 1-phosphate in the liver and renal proximal tubules. Table 1-12-4 compares the two conditions. Symptoms are reversed after removing fructose and sucrose from the diet. 

Table 15.4. Hereditary fructose intolerance (fructose-1-phosphate aldolase deficiency) ...

S. M. Aronson, and S. M. Saieer Fructose-1-phosphate aldolase deficiency in Tay-Sachs disease. Amer. J. Med. 36, 481 (1964). 

The aldolase that cleaves fructose phosphates is deficient. Fructose 1-phosphate accumulates and inhibits glucose production, causing severe hypoglycemia if fructose is ingested. 

Fructose-bisphosphate aldolase, which also acts on fructose-1-phosphate, is the enzyme deficient in hereditary fructose intolerance (HFI, MIM 229 600). 

DHAP is a glycolysis intermediate, whereas glyceraldehyde must be reduced by a mitochondrial enzyme, glyceraldehyde dehydrogenase, to glycerol, which is then subject to action by glycerol kinase in the liver. The aldolase seems to be the principal pathway of metabolizing fructose and depends on the initial phosphorylation step catalyzed by fructokinase, which produces fructose-l-phosphate. Fructokinase is defective in an inherited disorder, essential fructosuria. Fructose-l-phosphate aldolase is deficient in the hereditary disorder fructose intolerance. 

A deficiency of fructose-1-phosphate aldolase produces this rare disorder with hypoglycemia and liver failure. Fructose ingestion inhibits glycogenolysis and giuconeogenesis, producing hypoglycemia. Early detection is important because this condition responds to a diet devoid of sucrose and fructose. 

The molecular basis of HFI involves the deficiency of normal D-fructose 1-phosphate aldolase activity, and low activity of D-fructose 1,6-bisphosphate aldolase in liver, intestine, and renal cortex. Accumulated D-fructose 1-phosphate leads to a diminution of liver-glycogen phosphorylase activity, causing severe hypoglycemia. An accumulation of D-fructose 1-phosphate produces renal acidification and subcellular pathology of the jejunum and liver. 

It is now well established that great majority of cases of TSD occur in Jewish families. Exceptions were reported by Falkenheim (1901), Starck (1920), Catel (1943), Aronson et al. (1960). Probably, the incidence of TSD in races other than the Jewish would actually be even smaller than reported wdth more complete knowledge of the type of amaurotic family idiocy in some subjects and of the ancestry in others. 90% of 219 Tay-Sachs children of Aronson and Volk (1962) belonged to the Jewish race as jugded by their religion. TSD in Japanese families was reported by Cordes and Horner (1929) and Murakami (1957). From epidemiologic studies on the frequency of a deficiency of fructose-1-phosphate aldolase (Volk et al. 1964), the incidence of TSD in Jews is 100 times that of non-Jews. This is discussed in more detail in the chapter by Fuhrmann. 

Of great interest is the discovery of a deficiency or absence of fructose-1-phosphate aldolase in TSD serum (Volk et al. 1964). The enzyme, which normally catalyzes the splitting of fructose-1-phosphate into two three-carbon compounds which then gain access to the glycolytic pathway, was determined by a modi-... 

Hereditary fructose intolerance which is a more serious condition in which there are metabolic disturbances, e.g. hypoglycaemia, after fructose ingestion. It is due to a deficiency of the enzyme fructose-1-phosphate aldolase. 

Fructose intolerance A genetic deficiency in the liver enzyme aldolase B. The absence of this enzyme leads to a build up of fructose 1-phosphate and depletion of liver ATP and phosphate stores. 

In the liver, kidney, and intestine, fructose can be converted to glycolytic/ gluconeogenic intermediates by the actions of three enzymes—fructokinase, aldolase B, and triokinase (also called triose kinase)—as shovra in Figure 24-1. In these tissues, fructose is rapidly phosphorylated to fructose 1-phosphate (FIP) by fructokinase at the expense of a molecule of adenosine triphosphate (ATP). This has the effect of trapping fructose inside the cell. A deficiency in this enzyme leads to the rare but benign condition known as essential fmcto-suria. In other tissues such as muscle, adipose, and red blood cells, hexokinase can phosphorylate fructose to the glycolytic intermediate fmctose 6-phosphate (F6P). 

---