The report by Wenzel and colleagues highlights the risks inherent in fructose tolerance testing and the challenges accompanying evaluation for hereditary fructose intolerance (HFI) (1). The rapid resuscitative intervention after fructose exposure described by the authors may have saved the child’s life, and the authors should be commended for subsequent expeditious diagnosis of a rare disease. Nevertheless, a prospective consideration of the patient’s history could have raised concern for HFI before fructose tolerance testing. Historically, the diagnosis of HFI was made by invasive and dangerous analyses, such as measurement of hepatic aldolase B activity or intravenous fructose tolerance testing. The reliability of enzyme analysis may be questionable, considering a report describing “transient hereditary fructose intolerance” (2) and our own experience with variable aldolase B activity in a patient considered for HFI, which together raise the concern that single measurements of low enzyme activity may have poor diagnostic specificity. The potential dangers of intravenous fructose infusion are illustrated by the reports of fatalities associated with the provision of fructose-based parenteral nutrition. These tests have largely given way to genetic approaches for diagnosing HFI. The identification of aldolase B mutations associated with HFI has led to PCR-based strategies that provide estimated diagnostic sensitivity of >95%. Such tests have also been used to estimate the population prevalence of HFI. Interestingly, these estimates (approximately 1 in 20 000 Caucasian individuals) are much higher than our own clinical experiences suggest, raising the possibility that HFI may often be undiagnosed. With these considerations in mind, many investigators now discourage fructose tolerance testing because of concern about the potential for severe toxicity and even death. This case reminds us of those dangers and supports the use of molecular genetic analysis whenever HFI is considered a possibility. Even when genetic analysis is uninformative, many do not use fructose tolerance testing but instead prefer dietary avoidance of fructose as a safer approach to assess the possible contributions of fructose on the symptoms of concern.
Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.
Authors’ Disclosures of Potential Conflicts of Interest: No authors declared any potential conflicts of interest.
Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript.
- © 2009 The American Association for Clinical Chemistry