AJM onlineReviewOrthopedic Manifestations of Ochronosis: Pathophysiology, Presentation, Diagnosis, and Management
Section snippets
Pathophysiology
A functioning HGD enzyme splits the aromatic ring of homogentisic acid, a product of tyrosine and phenylalanine metabolism.7, 8, 9 Homogentisic acid can polymerize and form the brown/black ochronotic pigment that is often seen in the clinical manifestations of the disease. In patients with alkaptonuria, the excess homogentisic acid accounts for the clinical triad of alkaptonuria (excess homogentisic acid oxidizes and turns dark on standing), ochronosis (homogen-tisic acid oxidation products
Presentation
Because of the rarity of the disease and paucity of clinical symptoms until middle age, the diagnosis of alkaptonuria occasionally is discovered intraoperatively in patients undergoing joint replacement surgery through the observation of the characteristic bluish-black discoloration of the tissue surrounding the joint.1, 4 Although these symptoms appear later in life, connective tissue degeneration is rapid and aggressive, often leading to the need for joint replacement.8 Clinical involvement
Diagnosis
Darkening of the urine is a common diagnostic feature of alkaptonuria, and it is often the only defining feature to appear in children with the disease.1 Therefore, screening for alkaptonuria should be considered in children whose parents report that they are producing unusually dark urine. The disease can be detected in children as young as a few months of age by the presence of dark spots in the diapers or underwear, but the parents of affected children routinely overlook this sign. Because
Management
Kara et al17 summarize current treatment options as including the administration of nonsteroidal anti-inflammatory drugs and preparations containing glucosamine and chondroitin sulfate, intra-articular injection of hyaluronic acid and steroids, arthroscopic debridement of the affected joint, and arthroplasty.17 Currently, there is no proven therapy or prophylactic treatment for alkaptonuric patients. Treatment is generally supportive and aimed at preventing or minimizing the effects of
Perioperative Management
Pandey et al23 systematically outlined the perioperative concerns and implications for patients with alkaptonuria undergoing arthroplasty. Careful positioning and padding of pressure points should be considered to avoid triggering pain in other affected joints. Preoperative neurologic examination and navigation of difficult regional blocks should be considered given the degenerative changes in the spine. It is recommended to fully evaluate the patient's extent of systemic dysfunction when
Prevention
Aims at prevention are focused on limiting the progression of ochronotic arthropathy. Restriction of dietary protein, particularly tyrosine and phenylalanine, is controversial. It has been shown to limit homogentisic acid excretion in children; however, the data showed less success in adolescents and adults, given their deteriorating dietary compliance.8, 9, 10 Vitamin C (up to 1 g/d) often is recommended because of its effect on urinary excretion of homogentisic acid, as well as the observable
Conclusions
Ochronotic arthropathy is a rare outcome in patients with alkaptonuria, manifesting first in the intervertebral discs of the lumbar spine, with subsequent degeneration most often observed in the knee, hip, and shoulder joints. Efforts at treatment are targeted at minimizing the damaging effects of the underlying metabolic disorder on the articular cartilage. Vitamin E and N-acetyl cysteine are potential therapies because of their scavenging of free radicals and consequent limitation of
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Conflict of Interest: None.
Authorship: All authors had access to the data and played a role in writing this manuscript.