Inborn errors of fructose metabolism

Abstract Most people in developed countries ingest 50 to 100 g fructose equivalents daily in their diet, arising from fructose itself, sucrose, and sorbitol. After rapid carrier-mediated absorption across the intestinal epithelium, fructose is metabolized (mainly in the liver) by the enzymes ketohexokinase (fructokinase), aldolase B, and triokinase, eventually being converted into glucose or glycogen. Dietary sugars—burgeoning constituents in food and drinks worldwide—have undesirable effects on those with limited capacity to metabolize fructose, including severe illness or death in young patients. ‘Fructose malabsorption’ describes incomplete absorption of fructose that is associated with abdominal symptoms and diarrhoea reminiscent of intestinal disaccharidase deficiency. Symptoms occur after ingestion of fructose- or sorbitol-rich foods and drinks such as apple juice, but as yet a convincing genetic cause for this condition has not been found. Symptoms improve when the offending sugars are avoided. Three inborn errors of fructose metabolism are recognized and these disorders are vivid examples of gene–environment interactions: (1) essential or benign fructosuria due to fructokinase deficiency—a very rare disorder with apparently no ill effects; (2) hereditary fructose intolerance (fructosaemia)—an autosomal recessive disease caused by deficiency of aldolase B; and (3) fructose-1,6-diphosphatase deficiency —a very rare disease of infancy and childhood associated with failure of hepatic gluconeogenesis causing bouts of severe hypoglycaemia, ketosis, and lactic acidosis provoked by infection and starvation.