Degenerative Osteoarthritis with Multiple Joint Arthroplasties Due to Alkaptonuria, a Rare Inborn Error of Tyrosine Metabolism (original) (raw)

Alkaptonuria with extensive ochronotic degeneration of the Achilles tendon and its surgical treatment: a case report and literature review

Asian Biomedicine

Background Alkaptonuria is a rare genetic metabolic disorder due to deficiency of homogentisate 1,2-dioxygenase (HGD), an enzyme catalyzing the conversion of homogentisate to 4-maleylacetoacetate in the pathway for the catabolism of phenylalanine and tyrosine. HGD deficiency results in accumulation of homogentisic acid and its pigmented polymer. Ochronosis is a bluish-black discoloration due to the deposition of the polymer in collagenous tissues. Extensive ochronotic involvement of the Achilles tendon in alkaptonuria and its surgical treatment is rarely reported. Case report A 43-year-old man presented to our clinic in March 2019 with sudden onset of left Achilles tendon pain with no history of prior trauma. Surgical exploration revealed a complete disruption of the tendon at its attachment to the calcaneus. Black pigmentation was extensive and reached the calcaneal tuberosity, extending about 7 cm from the insertion. Discussion Achilles reconstruction was performed using flexor ha...

Cartilage biomarkers in the osteoarthropathy of alkaptonuria reveal low turnover and accelerated ageing

Rheumatology (Oxford, England), 2017

Alkaptonuria (AKU) is a rare autosomal recessive disease resulting from a single enzyme deficiency in tyrosine metabolism. As a result, homogentisic acid cannot be metabolized, causing systemic increases. Over time, homogentisic acid polymerizes and deposits in collagenous tissues, leading to ochronosis. Typically, this occurs in joint cartilages, leading to an early onset, rapidly progressing osteoarthropathy. The aim of this study was to examine tissue turnover in cartilage affected by ochronosis and its role in disease initiation and progression. With informed patient consent, hip and knee cartilages were obtained at surgery for arthropathy due to AKU (n = 6; 2 knees/4 hips) and OA (n = 12; 5 knees/7 hips); healthy non-arthritic (non-OA n = 6; 1 knee/5 hips) cartilages were obtained as waste from trauma surgery. We measured cartilage concentrations (normalized to dry weight) of racemized aspartate, GAG, COMP and deamidated COMP (D-COMP). Unpaired AKU, OA and non-OA samples were c...

Ochronotic Arthropathy with Severe Articular Involvement Necessitates Total Joint Replacement

HIP International, 2006

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. Alkaptonur...

Alkaptonuric Ochronosis Superimposed With Septic Arthritis in a Middle-aged Man

2020

Alkaptonuria is a rare inborn metabolic disease, in which an enzymatic deficiency accumulates alkapton in different tissues, causing darkness and injury, especially in spine and large cartilages, called ochronosis. The urine darkness can be a key to early diagnosis in childhood, but some cases are missed until adulthood and gradual damage to cartilages causes disability and impairs the patients’ quality of life. Here, a 49-year old male patient is presented with a 2 week history of left knee pain and swelling, who underwent arthrotomy, and the macro- and microscopic evaluation revealed ochronosis, superimposed by septic arthritis. Diagnosis of this rare disease should be considered in differential diagnoses of common joint disorders, like septic arthritis and osteoarthritis, so that appropriate management of the disease can prevent further damages.

Alkaptonuria in a middle-aged female

Caspian Journal of Internal Medicine, 2012

Background: Alkaptonuria (AKU) or ochronosis is a rare progressive degenerative arthropathy that results from deficiency of enzyme homogentisate 1,2 dioxygenase (HGD). The features include arthritis of the spine and in larger peripheral joints, with chondrocalcinosis. In this paper, we present a case of alkaptonuria in a 54 year old woman in Tehran, Iran. Case Presentation: A 54 year old woman with pain and limitation of motion in hip and lumbar spine was admitted in Firoozgar Hospital, Tehran. The problem began about 12 years ago with a history of darkening of urine and discoloration of sclera and ears. In imaging studies, there were degenerative changes in spine. In urine examination, the darkening of urine after exposure to air or bicarbonate found. Alkaptouria was confirmed by demonstrating an increased homogentisic acid (HGA) in urine. Her sister had back pain for a long period of time without response to therapy. She was subsequently diagnosed with alkaptonuria. Conclusion: Alkaptonuria must be considered in the evaluation of low back pain of patients especially with having a positive family history and bluish discoloration of cartilage tissues.

Ochronotic arthropathy-a rare clinical case

Oxford medical case reports, 2018

Ochronotic arthropathy is a rare condition found in patients with alkaptonuria that results from the accumulation of ochronotic pigment. We present the case of a 65-year-old woman who presented for medical evaluation due to hip and knee chronic pain. The physical and radiographic findings were compatible with an end-stage hip osteoarthritis and knee osteoarthritis. During total hip arthroplasty it was noticed that the articular capsule and the cartilage of the femoral head were black. In the postoperative period she was diagnosed with alkaptonuria. Later, a total knee arthroplasty was performed and once more the presence of black cartilage was noted. Alkaptonuria usually appears after age 30 and is usually asymptomatic until the involvement of the spine, hip, knee and shoulder joints. Therefore, orthopaedic surgeons must be suspicious of an atypical arthropathy in order to not be overwhelmed during surgery with the presence of darkened cartilage.

Homogentisate 1, 2 dioxygenase is expressed in human osteoarticular cells: Implications in alkaptonuria

Journal of cellular …, 2012

Alkaptonuria (AKU) results from defective homogentisate1,2-dioxygenase (HGD), causing degenerative arthropathy. The deposition of ochronotic pigment in joints is so far attributed to homogentisic acid produced by the liver, circulating in the blood and accumulating locally. Human normal and AKU osteoarticular cells were tested for HGD gene expression by RT-PCR, mono- and 2D-Western blotting. HGD gene expression was revealed in chondrocytes, synoviocytes, osteoblasts. Furthermore, HGD expression was confirmed by Western blotting, that also revealed the presence of five enzymatic molecular species. Our findings indicate that AKU osteoarticular cells produce the ochronotic pigment in loco and this may strongly contribute to induction of ochronotic arthropathy. J. Cell. Physiol. 227: 3254–3257, 2012. © 2011 Wiley Periodicals, Inc.