Hereditary Fructose Intolerance (HFI) (Fructose 1-Phosphate Aldolase Deficiency) Workup

Updated: Oct 15, 2019
  • Author: Karl S Roth, MD; Chief Editor: Maria Descartes, MD  more...
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Workup

Laboratory Studies

Based on the thorough dietary history of an ill child, the most straightforward approach to diagnosis of fructose 1-phosphate aldolase deficiency is to demonstrate the presence of a non–glucose-reducing sugar in the urine. This is readily accomplished with Clinitest. Then, if test results are positive, thin-layer chromatographic separation should be used for confirmation.

Urine metabolic screening results may also provide evidence of glucosuria, proteinuria, and aminoaciduria, all of which are part of renal Fanconi syndrome.

Plasma electrolyte levels are important to determine, because the renal tubular acidosis component of hereditary fructose intolerance (HFI) may significantly depress the total plasma bicarbonate level.

Obtain liver function test results to assess the degree of hepatocellular disease.

Molecular genetic testing is recommended to establish the nature of the biallelic ALDOB mutations and to provide the basis for prenatal testing. There is debate about the need for the latter, but the difficulties encountered with attempts to completely eliminate dietary sources of fructose may warrant it.

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Other Tests

Elimination of dietary fructose is both a compulsory and therapeutic step. In patients who are ill, elimination may also serve as a diagnostic test because all symptoms should completely resolve.

Only asymptomatic patients in a controlled setting should undergo intravenous fructose tolerance testing; oral fructose tolerance testing should be avoided because of the potentially violent GI response.

The combination of a therapeutic response to fructose elimination and a positive response to the fructose tolerance test is sufficient to exclude obtaining a biopsy sample. However, a molecular analysis in leucocytes of the gene on chromosome 9 may provide definitive evidence of a mutation at the q22.3 band.

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Histologic Findings

In a liver biopsy specimen from an untreated patient, evidence of hepatocellular involvement is clear, including areas of focal necrosis, fatty degeneration in peripheral lobules, bile duct proliferation, and late changes of portal and biliary cirrhosis. Biopsy of the liver should not be undertaken as a diagnostic procedure, except in cases of demonstrable liver disease.

Histologic changes are much less striking in the kidney and intestine, the other tissues with aldolase-B deficiency.

The kidney may demonstrate granulation of the proximal tubular epithelium with some tubule dilatation.

The intestine may show small areas of hemorrhage in the submucosa or serosa.

Except in untreated patients with cirrhosis late in the course of disease, all of the above changes are reversible. Of note, the availability of molecular analysis of the gene defect obviates the need for a corroborative biopsy sample.

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