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The biochemical basis of hereditary fructose intolerance

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Journal of Inherited Metabolic Disease

Abstract

Hereditary fructose intolerance is a rare, but potentially lethal, inherited disorder of fructose metabolism, caused by mutation of the aldolase B gene. Treatment currently relies solely on dietary restriction of problematic sugars. Biochemical study of defective aldolase B enzymes is key to revealing the molecular basis of the disease and providing a stronger basis for improved treatment and diagnosis. Such studies have revealed changes in enzyme activity, stability and oligomerisation. However, linking these changes to disease phenotypes has not always been straightforward. This review gives a general overview of the features of hereditary fructose intolerance, then concentrates on the biochemistry of the AP variant (Ala149Pro variant of aldolase B) and molecular pathological consequences of mutation of the aldolase B gene.

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Abbreviations

ATP:

Adenosine triphosphate

AP-aldolase:

Ala149Pro variant of aldolase B

ARMS:

Amplification refractory mutation system

DHAP:

Dihydroxyacetone phosphate

GKRP:

Glucokinase regulatory protein

HFI:

Hereditary fructose intolerance

F 1-P:

Fructose 1-phosphate

OMIM:

Online Mendelian Inheritance in Man

PDB:

Protein Data Bank

RFLP:

Restriction fragment-length polymorphism

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Acknowledgements

We thank the anonymous referees for many valuable suggestions. NB gratefully acknowledges the support of the Arthritis Research Campaign (UK).

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Authors and Affiliations

  1. School of Biological Sciences, Queen’s University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast, BT9 7BL, UK

    Nadia Bouteldja & David J. Timson

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  1. Nadia Bouteldja
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  2. David J. Timson
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Correspondence to David J. Timson.

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Communicated by: Gerard T. Berry

References to electronic databases: OMIM: 229600, EC: 4.1.2.13

Competing interest: None declared.

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Bouteldja, N., Timson, D.J. The biochemical basis of hereditary fructose intolerance. J Inherit Metab Dis 33, 105–112 (2010). https://doi.org/10.1007/s10545-010-9053-2

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