The promising new drug nitisinone lowers HGA levels by reversibly inhibiting the HGAproducing enzyme (4-hydroxyphenyl)pyruvate dioxygenase (HPPD) . While nitisinone treatment can arrest ochronosis , it cannot reverse it. Moreover, the FDA considers HGA elevation a biomarker but not a cause of ochronosis in AKU , with the result that nitisinone is thus far not approved for patients in the US. Therefore, there is a need to conclusively establish a link from HGA elevation to the cartilage degradation seen in ochronosis.