Related Experiment Videos
The diagnosis of hereditary fructose intolerance
Insights
Hereditary fructose intolerance (HFI) diagnosis is improved by the intravenous fructose tolerance test (FTT). This test reliably distinguishes HFI from other conditions, aiding in early dietary management for this serious disorder.
Area of Science:
- Metabolic disorders
- Pediatric gastroenterology
- Clinical diagnostics
Background:
- Hereditary fructose intolerance (HFI) is a serious metabolic disorder requiring prompt diagnosis.
- Nutritional history is crucial for suspecting HFI.
- Diagnostic accuracy for HFI can be enhanced through specific clinical tests.
Purpose of the Study:
- To evaluate the diagnostic utility of the intravenous fructose tolerance test (FTT) for Hereditary fructose intolerance (HFI).
- To compare the FTT with liver aldolase assays in diagnosing HFI.
- To establish reliable diagnostic protocols for HFI.
Main Methods:
- Conducted intravenous fructose tolerance tests (FTT) on 11 children and 6 adults with HFI, along with age-matched controls.
- Monitored blood glucose, phosphorus, urate, magnesium, and fructose levels for two hours post-infusion.
- Performed enzymatic assays on liver biopsies from 35 children with HFI and controls, assessing fructaldolase and reference enzymes.
Main Results:
- The intravenous FTT reliably differentiated HFI individuals from controls and those with other liver diseases.
- Children with HFI exhibited more pronounced hypoglycemia on FTT compared to adults.
- Liver aldolase deficiency was present in HFI patients, but also in some non-HFI liver disease cases, necessitating additional enzyme assays and histology for definitive diagnosis.
Conclusions:
- The intravenous FTT is a reliable, simple, and safe diagnostic tool for HFI when performed in a hospital setting.
- Diagnosis of HFI requires a combination of dietary history, FTT, and potentially liver biopsy with enzymatic analysis.
- Recommended diagnostic steps include fructose elimination, FTT after withdrawal, and laparoscopic liver biopsy if uncertainty persists.
Abstract:
Hereditary fructose intolerance (HFI) is a potentially life-threatening disorder and can be suspected from a detailed nutritional history. The usefulness of 2 diagnostic procedures, fructose tolerance test (FTT) and aldolase assay on biopsied liver, was studied. A standardized intravenous FTT with 200 mg/kg b.w. was done on 11 children with HFI, 17 age-matched contrast children, 6 adults with HFI and 6 adult controls. Blood glucose, phosphorus, urate, magnesium and fructose were followed for 2 hours. By the FTT, each HFI individual was reliably distinguished from controls and contrasts and even from those with acute liver disease other than HFI. Both children with non-HFI hepatopathy examined by both procedures had a normal FTT in spite of reduced liver fructaldolase activity. HFI children responded to the FTT by earlier and more pronounced hypoglycemia than adults, and one girl converted to an adult type response between the ages 12 and 181/2 years. Responses of two HFI sibling pairs and of one set of monozygotic twins were typical for age, but resemblance was no greater than within the unrelated HFI probands. The intravenous FTT is judged a reliable diagnostic tool, simple and harmless if done in hospital. Essential fructosuria is readily diagnosed by the FTT, but fructose-1,6-diphosphatase deficiency and HFI are not differentiated with certainty. Liver biopsies were obtained from 35 children with HFI, 14 contrast persons and 10 controls (of which 9 organ donors) and examined enzymatically. Deficiency of fructaldolase was observed in all HFI children but also in some contrast children suffering from acute liver disease other than HFI. In these, HFI could only be excluded when the reduced activity of reference enzymes such as fructose-1,6-diphosphatase and glucose-6-phosphatase and liver histology were included in the evaluation. In one deceased HFI infant, fructaldolase was deficient in both, liver and kidney cortex. Extent of antibody activation and of heat inactivation of residual fructaldolase varied between unrelated HFI patients but not within families. These results did not contribute to diagnosis but further documented genetic heterogeneity of HFI. For diagnosis of HFI we recommend 1. immediate elimination of fructose from the diet, 2. the intravenous FTT after several weeks of fructose withdrawal, and 3., should diagnosis still be uncertain, laparoscopic liver biopsy for assay of fructaldose and of reference enzymes and for histology.