Metabolomic Studies in the Inherent Failure of Alkaptonuria Metabolism show Biological changes in Tyroleum Metabolism

Alkaptonuria (AKU) is an inherited disorder of tyrosine metabolism caused by lack of active enzyme homogentisate 1,2-dioxygenase (HGD). The primary consequence of HGD deficiency is increased circulating homogentisic acid (HGA), the main agent in the pathology of AKU disease. Here we report the first metabolomics analysis of AKU homozygous Hgd knock out (Hgd/) mice to model the wider metabolic effects of Hgd deletion and the implication for AKU in humans. Untargeted metabolic profiling was performed on urine from Hgd /AKU (nZ15) and Hgdþ/non-AKU control (nZ14) mice by liquid chromatography high-resolution time-of-flight mass spectrometry (Experiment 1). The metabolites showing alteration in Hgd/were further investigated in AKU mice (nZ18) and patients from the UK.