Hereditary fructose intolerance.

Abstract

Hereditary fructose intolerance (HFI, OMIM 22960), caused by catalytic deficiency of aldolase B (fructose-1,6-bisphosphate aldolase, EC 4.1.2.13), is a recessively inherited condition in which affected homozygotes develop hypoglycaemic and severe abdominal symptoms after taking foods containing fructose and cognate sugars.

Hereditary fructose intolerance: functional study of two novel ALDOB natural variants and characterization of a partial gene deletion

“…However, even in these cases, HFI remains a problem due to recurrent inadvertent fructose ingestion. Deaths have been documented in undiagnosed HFI individuals who have been challenged unintentionally with fructose (or cognate sugars), for example, in parenteral feeding [Ali et al, 1998]. …”

A Six-month-old infant with liver steatosis

“…These intermediate trioses are incorporated directly into either the glycolytic pathway (eventually forming lactate and pyruvate to act as substrate for the Krebs cycle) or the gluconeogenic pathway to form glucose or glycogen. 14 In HFI, ingestion of fructose results in an exaggerated accumulation of fructose-1-phosphate and depletion of the intracellular pool of inorganic phosphate and guanosine triphosphate and hence adenosine triphosphate (ATP). 14 The reduced phosphate concentration activates adenosine deaminase, 15,16 resulting in degradation of purine nucleotides to uric acid, 17 producing the characteristic hyperuricemia of HFI.…”

“…14 In HFI, ingestion of fructose results in an exaggerated accumulation of fructose-1-phosphate and depletion of the intracellular pool of inorganic phosphate and guanosine triphosphate and hence adenosine triphosphate (ATP). 14 The reduced phosphate concentration activates adenosine deaminase, 15,16 resulting in degradation of purine nucleotides to uric acid, 17 producing the characteristic hyperuricemia of HFI. The hypoglycemia seen in HFI results from defects in both glycogenolysis and gluconeogenesis, which are thought to be secondary to inhibition by excessive fructose-1-phosphate.…”

“…The hypoglycemia seen in HFI results from defects in both glycogenolysis and gluconeogenesis, which are thought to be secondary to inhibition by excessive fructose-1-phosphate. 18,19 Impairment of gluconeogenesis combined with fructose-1-phosphate activation of pyruvate kinase 14,20 results in accumulation of Krebs cycle precursors alanine, lactate, and pyruvate, which contribute to the metabolic acidosis seen in HFI. This is exacerbated by the proximal renal tubular acidosis (Fanconi syndrome) where aminoaciduria, phosphaturia, and wasting of bicarbonate occurs, as seen in our case.…”

“…Another possibility is that phenotypic variability exists, although experts in this field maintain that disease severity relates less to genotype than to the individual dietary exposure. 14 The source of fructose, the cause of his deterioration, was from both the soya formula (Alsoy, Nestle) and particularly the Portagen (Mead Johnson Nutritionals) that he had been given, both of which contain carbohydrate as sucrose, which is broken down to fructose and glucose in the gut. His prior diet also contained some fructose in fruit and vegetables although he was not symptomatic, which probably relates to the amount of substrate he was exposed to and possibly to his residual enzyme activity.…”