• Free fructose is the main ingredient of fruits, vegetables and honey. It is metabolized mainly in the liver and to a lesser extent in the intestines and kidneys. The main pathway in fructose metabolism is the conversion of fructose to fructose-1-phosphate by the fructokinase enzyme, and this to glyceraldehyde and dehydroxyacetone phosphate by the action of fructose-1-phosphate aldolase. Later, these trioses are converted to either pyruvate, citric acid cycle, or glucose or glycogen.
• Fructose metabolism diseases are autosomal recessive.
Essential (Benign) fructosuria:
• It is a rare automosal recessive disease that occurs with fructokinase deficiency. The enzyme deficiency is mainly in the liver and additionally in the intestinal and renal cortex.
• Does not cause clinical findings (90% of the accumulated fructose is metabolized by fructose-6-phosphate in the adipose tissue).
• Diagnosis is made by positivity of reducing substance in urine and sugar chromatography.
• Treatment is unnecessary.
Hereditary Fructose Intolerance:
• It is an autosomal recessive disease due to Fructose 1-P aldolase (Fructaldolase=Aldolase B) deficiency.
• The accumulation in tissues of fructose-1-phosphate, which cannot be converted into trioses with the intake of foods containing fructose, causes toxic effects in the liver and kidney.
• Inhibition of enzyme activities for glycogenolysis and gluconeogenesis by fructose-1-phosphate accumulating in hepatocytes causes hypoglycemia unresponsive to glucagon.
• On the other hand, proximal tubular functions are also impaired due to fructose-1-phosphate accumulating in the kidneys {Renal Fanconi syndrome).
Clinic
• Early symptoms and signs are similar to galactosemia.
• Vomiting, inability to gain weight, jaundice, irritability and convulsions, which become especially evident after switching to complementary foods, are observed.
• While acute fructose intake causes hypoglycemia; liver disease and growth retardation are seen after chronic intake.
Diagnosis
• There are fructosuria, hypoglycemia, hypophosphatemia, hyperuricemia, hyperbilirubinemia, increase in transaminases, hypoalbuminemia, decrease in coagulation factors, proteinuria, aminoaciduria.
• Oral fructose tolerance test should not be performed due to the risk of developing acute severe attack (hypoglycemia, hypophosphatemia, hyperuricemia).
• Enzymatic diagnosis can be made by liver biopsy in patients with reducing substance and fructose in the urine. Although not in every case, the diagnosis can be made by mutation analysis in most patients.
Treatment
• It is the elimination of foods containing fructose, sucrose, sorbitol from the diet.
• Generally, mental retardation is not seen.
Fructose 1,6-Diphosphatase Deficiency:
• Fructose 1,6-diphosphatase deficiency is in liver, kidney and jejunum. Muscle fructose 1,6-diphosphatase is controlled by different gene.
• It is one of the four enzymes found in the liver and involved in gluconeogenesis. Its deficiency inhibits gluconeogenesis, but glycogenolysis is intact. Hypoglycemia in prolonged fasting, lactic acidosis, normal liver and kidney functions, and not being disturbed when eating sugary foods are the findings that distinguish it from hereditary fructose intolerance.
• Fructose is reduced but not removed from the diet.
Renal Fanconi Syndrome
It occurs as a result of generalized transport dysfunction in the proximal tubule.
• Glucosuria
• Phosphaturia (hypophosphatemic rickets}
• Generalized aminoaciduria
• Bicarbonaturia (proximal RTA}
• Proteinuria, polyuria, polydipsia
• Moreover; potassium, protein, uric acid are lost in the urine.
Metabolic diseases that cause Fanconi syndrome:
• Cystinosis (Most common)
• Tyrosinemia Type I
• Glycogen storage disease type I and XI
• Galactosemia
• Hereditary fructose intolerance
Metabolic diseases causing diffuse hepatocellular damage:
• Galactosemia
• Hereditary fructose intolerance
• Tyrosinemia Type-I
• Wilson's disease
• Alpha-I antitrypsin deficiency
• Respiratory chain diseases in newborns