HFI Laboratory at Boston University

National Instituteof Health Sponsored HFI Research

The National Institute of Diabetes, and Digestive and Kidney Diseases has funded our research on hereditary fructose intolerance for over 23 years. The abstract for the most recent support can be viewed by clicking here. The most recent work has three goals:

1) To define mutations responsible for hereditary fructose intolerance (HFI) in the American population, especially in those ethnic groups not previously studied. This is important because in order to diagnose a genetic disease using the mutations that cause the disease one has to know what most of the mutations are and how common each is. Otherwise, someone could have a HFI mutation and it would not be detected because scientists are unaware of it. Current standards require that a valid genetic test include a screen for 90% of all mutations for a given disease. For HFI, we now know only ~80% of ALL mutations and are able to routinely screen for those that comprise 75 – 95% but only among the Caucasian population.  These same mutations comprise only 5-60% of alleles in the African American, Asian American, and Hispanic population. More research is needed.

2) To answer questions regarding the pathology and physiology of the fructose normal metabolism and of the disease in an animal model. More understanding is needed.

3)  Past research determined the problem with the enzyme that is at the root of HFI for 80% of those who suffer.  Using this knowledge a chemical and computational search for drug candidates is being done that will possibly reverse the effects of the mutation.

4)  Those who suffer from HFI have revealed our lack of complete understanding of normal fructose metabolism.  Research is being done using bioinformatics and cell biology to define the physiological sites for fructose metabolism.

The investigations will: 1) determine the variety and prevalence of the mutations that cause this disease in America; 2) help to understand the biochemical roots of HFI caused by specific mutations, including any that affect expression of the aldolase gene, 3) provide insights into the structure and mechanism of this important enzyme by finding drug candidates that change its pathochemistry, and 4) establish an animal model in the mouse by gene-targeting technology. Eventually this animal model will help us understand the pathophysiology of the disease better and allow for trails of potential new treatments.

If you would like to become involved in our research, please email us at tolan@bu.edu.