305 INTRODUCTION Alkaptonuria (AKU) is an inherited metabolic disorder characterized by the absence of homogentisic acid oxidase (HGAO) enzyme. The absence of HGAO leads to the accumulation of homogentisic acid (HGA), produced during normal metabolism of phenylalanine and tyrosine, and to an autosomal recessive transmission. The gene for the enzyme production has been mapped on chromosome number 3 in the region of bands 3q21-q23. HGAO – a topologically complex structure – assembles a functional hexamer arranged as a dimer of trimers. Some authors have shown the intricate pattern of intra- and inter-subunit interactions, the extensive surfaces required for subunit folding and association. Furthermore, they have shown that this oligomeric enzyme can be inactivated at multiple levels by single-residue substitutions (1-4), hence explaining the predominance of missense mutations (67%) in AKU. Gene mutation determines the HGA and its polymers are not used and build up in the body. Some is excreted through the kidneys (4-8g/day) and causes urine darkening due to the oxidation of HGA; the rest is deposited in tissues, where it is toxic. The result is ochronosis, a brown/black Ochronotic arthropathy with severe articular involvement necessitates total joint replacement G. GASPARINI, S. CERCIELLO, M. VASSO, M. CILLO Department of Orthopaedics and Traumatology Catholic University of Rome, Rome - Italy ABSTRACT: The aim of this paper is to describe the pathological and clinical features of alkaptonuria (AKU). AKU clinical presentation is identified as ochronosis, the dark pigmentation of skin and cartilage that is caused by progressive accumulation of homogentisic acid (HGA) in connective tissues. We also discuss surgical considerations about joint replacement, which represents the only treatment in the case of severe articular degeneration. We report the case of a middle-aged female with both hip and knees affected. She underwent bilateral hip replacement and right knee arthroplasty. Preoperatively, the patient was examined clinically. Harris Hip Score (HHS) and Hospital for Special Surgery score (HSS) were completed for both hips, and for the right knee. Radiographs were made of both hips and the knee, in different projections. HHS for the left and right sides at the latest follow-up (11 and 9 years after surgery respectively) were 98 and 95. HSS 3.5 years after surgery was 97. Alkaptonuria is a rare inherited pathology caused by deficiency of the enzyme homogentisic acid oxidase (HGAO). Skeletal involvement is frequent and causes severe cartilage damage. HGA levels in blood and urine and articular symptoms make the diagnosis certain. Therapy is still debated: diet offers good results in young people while high doses of C vitamin seem to reduce the amount of deposits. Articular localizations usually lead to joint replacement. In this case functional and radiographic results are excellent even at long follow-up. (Hip International 2006; 16: 305-11) KEY WORDS: Ochronosis, Homogentisic acid, Joint replacement, Alkaptonuria Case Report Hip International / Vol. 16 no. 4, 2006 / pp. 305-311 © Wichtig Editore, 2006