OBJECTIVE: Alkaptonuria (AKU) is a rare, inherited disorder of tyrosine 
metabolism, where patients are unable to breakdown homogentisic acid (HGA), 
which increases systemically over time. It presents with a clinical triad of 
features; HGA in urine, ochronosis of collagenous tissues, and the subsequent 
ochronotic arthritis of these tissues. In recent years the advance in the 
understanding of the disease and the potential treatment of the disorder looks 
promising with the data on the efficacy of nitisinone. However, there are 
limited methods for the detection and monitoring of ochronosis in vivo, or for 
treatment monitoring. The study aim was to test the hypothesis that Raman 
spectra would identify a distinct chemical fingerprint for the non-ochronotic, 
compared to ochronotic cartilage.
DESIGN: Ochronotic and non-ochronotic cartilage from human hips and ears were 
analysed using Raman spectroscopy.
RESULTS: Non-ochronotic cartilage spectra were similar and reproducible and 
typical of normal articular cartilage. Conversely, the ochronotic cartilage 
samples were highly fluorescent and displayed limited or no discernible Raman 
peaks in the spectra, in stark contrast to their non-ochronotic pairs. 
Interestingly, a novel peak was observed associated with the polymer of HGA in 
the ochronotic cartilage that was confirmed by analysis of pigment derived from 
synthetic HGA.
CONCLUSION: This technique reveals novel data on the chemical differences in 
ochronotic compared with non-ochronotic cartilage, these differences are 
detectable by a technique that is already generating in vivo data and 
demonstrates the first possible procedure to monitor the progression of 
ochronosis in tissues of patients with AKU.