Orthopedic Manifestations of Ochronosis: Pathophysiology, Presentation, Diagnosis, and Management

Abstract

Ochronotic arthropathy occurs 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 oxidative damage to joint tissue. Arthroscopy has been found to be an effective diagnostic tool in cases of suspected ochronosis. Arthroplasty performed in patients with ochronotic arthropathy suggests that the procedure is effective in the alleviation of joint pain and the improvement of mobility. Perioperative management of these patients may require more careful consideration pertinent to the associated comorbidities of this disorder.

Misdiagnosis of alkaptonuria in an elderly patient

“…Degenerative spondylosis may be seen along the whole of the spine· however the most prominent involvement is in the lumbar region 15,18 . Tendon thickening and tears and joint effusions usually present later than 30 years of age 2 , as was the story with our case.…”

“…Kara et al 20 summarized the current treatment options including NSAIDs and preparations containing glucosamine and chondroitin sulfate, intra-articular injections of hyaluronic acid and steroids, arthroscopic debridement of the affected joint and arthroplasty 2,20 . Currently there is no established therapy or prophylactic treatment of alkaptonuria.…”

“…The gene encoding HGD has been maped to human chromosome 3q 21-q23 [3][4][5] . To date, more than 90 mutations of the HGD gene have been described, reflecting the disorder's clinical variability 2 . The inabitily to metabolise tyrosine and phenylalanine leads to HGA accumulation in the blood; the amount excreted in the urine turns dark brown or black on oxygenation or alkalinization 6,7 .This typical urine colour occurs early in the disease course but may not be noticed; fresh urine often seem normal and it may take several hours after voiding for the colour changes to occur.…”

“…Alkaptonuria (AKU) is a very rare inherited recessive autosomal metabolic disorder with an estimated prevalence ranging from 1:200.000 to 1:1000000 live births worldwide 1,2 ; it is caused by homogentisate 1,2-dioxygenase (HGD) deficiency, an enzyme responsible for converting homogentisic acid (HGA) to maleylacetoacetic acid in the tyrosine degradation pathway 1,2 . The gene encoding HGD has been maped to human chromosome 3q 21-q23 [3][4][5] .…”

Nitisinone: a review

“…[87][88][89] Ochronosis is a chronic process and clinical symptoms are typically observed from the second decade of life, including severe spondyloarthropathy, ruptures of the ligaments, tendons, and muscles; osteopenia, fractures; valvular heart disease; pigmentation of eyes and ears; central vein occlusion and elevated intraocular pressure; renal, prostatic, gallbladder, and salivary stones and renal insufficiency. 83,[90][91][92][93][94][95][96][97][98] Early degenerative ochronotic arthropathy is seen especially in weight-bearing joints, leading to severe pain in spine and large joints such as shoulder, hip, and knee. 98 Symptoms worsen from the fourth decade onward with progressive kyphoscoliosis and impaired spinal and thoracic mobility.…”