Clinical Chemistry and Laboratory Medicine

Alkaptonuria (AKU) is an inherited metabolic disease characterized by increased homogentisic acid (HGA) due to deficiency of homogentisate dioxygenase. Polymerisation of HGA via benzoquinone acetate, termed ochronosis, results in a black pigment in tissues, thereby altering their properties and leading to their degradation. The main consequences are

spondyloarthropathy, aortic valve disease, calculous disease, renal failure, fracture and ruptures of tendon, ligament and muscle. Treatment previously has been palliative employing analgesia and arthroplasty. A HGA-lowering therapy, nitisinone, is available for AKU, as it inhibits phydroxyphenylpyruvate dioxygenase. The optimal dose of nitisinone (10 mg daily) in AKU was confirmed in an European Union-funded study, SONIA 1, and is being applied in a 4-year outcomes study, SONIA 2. Nitisinone 2mg daily has also been used in the National AKU Centre in Liverpool off label since 2012. Data is presented in this meeting showing metabolic and nonmetabolic effects of nitisinone. Novel metabolic data addressing the metabolism in AKU is also presented.