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Frontiers in Medicine 2023Ochronosis is a rare autosomal recessive disorder of tyrosine metabolism characterized by multilevel spinal degeneration and arthritis of large weight-bearing joints,...
Ochronosis is a rare autosomal recessive disorder of tyrosine metabolism characterized by multilevel spinal degeneration and arthritis of large weight-bearing joints, which is referred to as ochronotic arthropathy. In this case report, we describe diagnosis and treatment of ochronotic arthropathy in a patient who underwent total hip arthroplasty (THA) and total knee arthroplasty (TKA). The Harris hip score was 26 preoperatively and 45, 68, 76, 90, 92, and 94 at 1, 3, 6, 9, 11, and 14 months, respectively, postoperatively. The forgotten joint score (FJS) of the hip was 27.8, 52.8, 81.1, 89.0, 90.6, and 92.4 at 1, 3, 6, 9, 11, and 14 months, respectively, postoperatively. TKA was performed 8 months after THA. The Knee Society Score was 36 before TKA and 74, 82, and 90 at 1, 3, and 6 months, respectively, after TKA. The FJS of the knee was 36.6, 63.9, and 84.5 at 1, 3, and 6 months, respectively, after TKA. The patient's knee range of motion returned to normal, with significant reduction in pain and improved satisfaction levels after TKA. THA and TKA can achieve good clinical outcomes in patients with ochronosis accompanied by severe joint pain.
PubMed: 37795417
DOI: 10.3389/fmed.2023.1212580 -
Journal of Orthopaedic Case Reports Jan 2023Ochronosis is a rare syndrome caused by accumulation of homogentisic acid in connective tissue due to deficiency of enzyme homogentisic acid oxidase. It characterized by...
INTRODUCTION
Ochronosis is a rare syndrome caused by accumulation of homogentisic acid in connective tissue due to deficiency of enzyme homogentisic acid oxidase. It characterized by blue-black pigmentation connective tissues such as sclera, cartilage of ear, and synovium of joints and it causes destruction of joints cartilage and early arthritis. Urine becomes dark coloured on prolonged standing. Some patient may develop rare cardiac manifestation due to accumulation of homogentisic acid on valves.
CASE REPORT
A 56-year-old female admitted with neck of femur fracture after history of fall at home. The patient was having chronic back ache and knee pain. Plain radiograph of knee and spine showed severe arthritic changes. Exposure during surgery was difficult due to hard and brittle tendons and capsule of joint. Femur head and acetabulum cartilage appeared dark brown. Dark brown pigmentation of sclera and hands was found on clinical examination postoperatively.
CONCLUSION
Patients with ochronosis usually develop early osteoarthritis and spondylosis which should be differentiated from other causes of early arthritis such as rheumatoid arthritis and seronegative arthritis. It leads to destruction of joint cartilage and weaking subchondral bone which leads to pathological fracture. And due to the stiffness of soft-tissues around joint, surgical exposure can be challenging.
PubMed: 37143563
DOI: 10.13107/jocr.2023.v13.i01.3498 -
Cureus Jan 2023Ochronosis is a rare metabolic disorder characterized by homogentisic acid deposition in the large joints and spine, resulting in progressive degeneration. We present...
Ochronosis is a rare metabolic disorder characterized by homogentisic acid deposition in the large joints and spine, resulting in progressive degeneration. We present two cases of ochronotic arthritis of the knee subjected to cemented total knee arthroplasty (TKA). These cases were diagnosed intraoperatively and later confirmed with a histopathologic examination. Orthopedic surgeons should be aware of the condition as the intraoperative finding of darkened cartilage might surprise them. After a five-year TKA follow-up, both of our cases showed better mobility and function.
PubMed: 36779093
DOI: 10.7759/cureus.33523 -
The American Journal of Case Reports Sep 2020BACKGROUND Alkaptonuria (AKU) is a rare metabolic disease caused by a deficiency in homogentisic acid oxidase, which leads to the accumulation of homogentisic acid dark...
BACKGROUND Alkaptonuria (AKU) is a rare metabolic disease caused by a deficiency in homogentisic acid oxidase, which leads to the accumulation of homogentisic acid dark pigments in tissues such as bones, ligaments, and tendons. Long-term duration of this condition, termed ochronosis, can result in degenerative arthropathy involving the spine and large joints. CASE REPORT This report describes a 55-year-old Jordanian woman presenting with chronic neck and lower back pain. History, physical examination, and radiological imaging indicated cervical myelopathy and lumbar spine degeneration. Two-level anterior cervical discectomy and fusion was performed successfully. Intra-operatively, the cervical discs were observed to be black, suggesting a diagnosis of alkaptonuria, which was later confirmed by genetic testing. A detailed history and physical examination revealed the absence of classical features of AKU. CONCLUSIONS Intraoperative detection of black disc material suggests the need for further tests to diagnose AKU, especially in indolent patients who did not have classical clinical features. Surgical management may improve outcomes in patients with cervical myelopathy due to ochronosis.
Topics: Alkaptonuria; Diskectomy; Female; Humans; Low Back Pain; Middle Aged; Ochronosis; Spinal Cord Diseases
PubMed: 32908119
DOI: 10.12659/AJCR.924575 -
Osteoarthritis and Cartilage Aug 2019Alkaptonuria (AKU) is a rare, inherited disorder of tyrosine metabolism, where patients are unable to breakdown homogentisic acid (HGA), which increases systemically...
OBJECTIVE
Alkaptonuria (AKU) is a rare, inherited disorder of tyrosine metabolism, where patients are unable to breakdown homogentisic acid (HGA), which increases systemically over time. It presents with a clinical triad of features; HGA in urine, ochronosis of collagenous tissues, and the subsequent ochronotic arthritis of these tissues. In recent years the advance in the understanding of the disease and the potential treatment of the disorder looks promising with the data on the efficacy of nitisinone. However, there are limited methods for the detection and monitoring of ochronosis in vivo, or for treatment monitoring. The study aim was to test the hypothesis that Raman spectra would identify a distinct chemical fingerprint for the non-ochronotic, compared to ochronotic cartilage.
DESIGN
Ochronotic and non-ochronotic cartilage from human hips and ears were analysed using Raman spectroscopy.
RESULTS
Non-ochronotic cartilage spectra were similar and reproducible and typical of normal articular cartilage. Conversely, the ochronotic cartilage samples were highly fluorescent and displayed limited or no discernible Raman peaks in the spectra, in stark contrast to their non-ochronotic pairs. Interestingly, a novel peak was observed associated with the polymer of HGA in the ochronotic cartilage that was confirmed by analysis of pigment derived from synthetic HGA.
CONCLUSION
This technique reveals novel data on the chemical differences in ochronotic compared with non-ochronotic cartilage, these differences are detectable by a technique that is already generating in vivo data and demonstrates the first possible procedure to monitor the progression of ochronosis in tissues of patients with AKU.
Topics: Adolescent; Adult; Aged; Alkaptonuria; Cartilage, Articular; Disease Progression; Ear Cartilage; Female; Hip Joint; Humans; Male; Middle Aged; Ochronosis; Spectrum Analysis, Raman; Young Adult
PubMed: 31022456
DOI: 10.1016/j.joca.2019.04.012 -
Cureus Aug 2023Alkaptonuria is a rare autosomal recessive trait. Symptomatic lumbar disc herniation warranting surgical intervention is a rare scenario in alkaptonuria and only a few...
Alkaptonuria is a rare autosomal recessive trait. Symptomatic lumbar disc herniation warranting surgical intervention is a rare scenario in alkaptonuria and only a few cases have been described in the literature. We present one such rare case of alkaptonuria in a 31-year-old female presenting with low back pain and left leg radiculopathy not relieved with conservative management. Roentgenograms of the lumbar spine revealed wafer-like disc calcifications and MRI showed a herniated disc at the L4-L5 level with deeply hypointense disc spaces in T2 suggestive of disc calcification and associated modic type 2 changes. During the surgery, the disc material removed was black in color, which raised a clinical suspicion of alkaptonuria. Postoperatively, the patient was re-examined and urine homogentisic acid was found to be raised. This, along with a histopathological examination, was diagnostic of alkaptonuria. The patient had excellent relief of symptoms postoperatively. In conclusion, if a 'black disc' is found during surgery, retrospective analysis and re-examination of patient clinical features and urine examination have to be done to diagnose alkaptonuria. While making a differential diagnosis of degenerative disc disease in patients with a calcified disc seen on radiography, a high index of suspicion for alkaptonuria has to be maintained.
PubMed: 37786570
DOI: 10.7759/cureus.44395 -
Orthopedic Research and Reviews 2023Alkaptonuric shoulder arthropathy is a challenging clinical entity in arthroplasty. In this report, we describe an atypical presentation, technical considerations, a...
IMPORTANCE
Alkaptonuric shoulder arthropathy is a challenging clinical entity in arthroplasty. In this report, we describe an atypical presentation, technical considerations, a literature review, and some recommendations of significant benefits to shoulder surgeons.
OBJECTIVE
The author's objective in this report is to illustrate the deleterious metabolic effects of ochronosis on cartilage and the development of early arthritis.
DESIGN
This is a case report study, done in May 2021.
SETTING
Middle East, Jordan.
INTRODUCTION
Alkaptonuria is a metabolic disease of amino acid metabolism that can affect multiple organ systems, including the musculoskeletal system. The musculoskeletal system manifestations usually involve the spine, knee, and, uncommonly, the shoulder. Tissue ochronosis caused by alkaptonuria can cause significant damage to the joint and surrounding soft tissue envelope. In this case, we presented a patient who has end-stage glenohumeral arthritis and rotator cuff arthropathy secondary to ochronosis.
CASE PRESENTATION
In this case report, we present a 42-year-old male patient who presented to the clinic with severe right shoulder pain and limitations of the range of motion, especially with abduction. The patient underwent radiographic assessment, which showed a rotator cuff arthropathy combined with advanced degenerative changes of the right glenohumeral joint. The patient underwent reverse total shoulder arthroplasty. After the surgery and on follow-up later on for a period of one year and after a period of physiotherapy and rehabilitation, the patient showed remarkable improvement in the pain and range of motion.
CONCLUSION
Alkaptonuria can have a detrimental effect on the articular cartilage and the surrounding soft tissue envelope, which might manifest clinically as early degenerative arthritis changes in a young adult patient. Shoulder involvement is extremely rare and can manifest with substantial injury to the glenohumeral joint; whenever such extensive damage is present, shoulder arthroplasty is the best treatment.
PubMed: 37091223
DOI: 10.2147/ORR.S402214 -
Journal of Orthopaedic Case Reports Oct 2021Alkaptonuria is a rare autosomal recessive metabolic disorder characterized by accumulation of homogentisic acid (HGA) due to an inherited deficiency of the enzyme HGA...
INTRODUCTION
Alkaptonuria is a rare autosomal recessive metabolic disorder characterized by accumulation of homogentisic acid (HGA) due to an inherited deficiency of the enzyme HGA oxidase. Unlike rheumatoid arthritis which affects the small joints of the hands and feet, ochronotic arthropathy predominantly involves the large weight-bearing joints such as hips, knees, and spine. The knee is the most common joint to be affected. Ochronotic arthropathy is usually managed conservatively, but for severely affected hip and knee joints, replacement is considered.
CASE REPORT
This report describes a case of 57-year-old male who presented with bilateral knee osteoarthritis who was incidentally diagnosed with ochronosis intraoperatively during total knee arthroplasty, its challenges faced and post-operative functional outcome after 18 months follow-up.
CONCLUSION
This case report highlights the need for high index of suspicion for preoperative diagnosis of ochronotic arthropathy. Difficult spinal anesthesia should be anticipated. Friable and stiff tendon due to ochronotic involvement can put the extensor tendon at risk of rupture during retraction of patella intraoperatively. Post-operative active quadriceps rehabilitation should be done with caution due to friable tendon.
PubMed: 35415103
DOI: 10.13107/jocr.2021.v11.i10.2464 -
Scientific Reports Nov 2022Alkaptonuria (AKU) is a rare inborn error of metabolism caused by a defective homogentisate 1,2-dioxygenase (HGD), an enzyme involved in the tyrosine degradation...
Alkaptonuria (AKU) is a rare inborn error of metabolism caused by a defective homogentisate 1,2-dioxygenase (HGD), an enzyme involved in the tyrosine degradation pathway. Loss of HGD function leads to the accumulation of homogentisic acid (HGA) in connective body tissues in a process called ochronosis, which results on the long term in an early-onset and severe osteoarthropathy. HGD's quaternary structure is known to be easily disrupted by missense mutations, which makes them an interesting target for novel treatment strategies that aim to rescue enzyme activity. However, only prediction models are available providing information on a structural basis. Therefore, an E. coli based whole-cell screening was developed to evaluate HGD missense variants in 96-well microtiter plates. The screening principle is based on HGD's ability to convert the oxidation sensitive HGA into maleylacetoacetate. More precisely, catalytic activity could be deduced from pyomelanin absorbance measurements, derived from the auto-oxidation of remaining HGA. Optimized screening conditions comprised several E. coli expression strains, varied expression temperatures and varied substrate concentrations. In addition, plate uniformity, signal variability and spatial uniformity were investigated and optimized. Finally, eight HGD missense variants were generated via site-directed mutagenesis and evaluated with the developed high-throughput screening (HTS) assay. For the HTS assay, quality parameters passed the minimum acceptance criterion for Z' values > 0.4 and single window values > 2. We found that activity percentages versus wildtype HGD were 70.37 ± 3.08% (for M368V), 68.78 ± 6.40% (for E42A), 58.15 ± 1.16% (for A122V), 69.07 ± 2.26% (for Y62C), 35.26 ± 1.90% (for G161R), 35.86 ± 1.14% (for P230S), 23.43 ± 4.63% (for G115R) and 19.57 ± 11.00% (for G361R). To conclude, a robust, simple, and cost-effective HTS system was developed to reliably evaluate and distinguish human HGD missense variants by their HGA consumption ability. This HGA quantification assay may lay the foundation for the development of novel treatment strategies for missense variants in AKU.
Topics: Humans; Alkaptonuria; Homogentisate 1,2-Dioxygenase; Dioxygenases; Polymorphism, Single Nucleotide; High-Throughput Screening Assays; Escherichia coli; Homogentisic Acid
PubMed: 36376482
DOI: 10.1038/s41598-022-23702-y -
Indian Journal of Dermatology,... Jul 2023
PubMed: 37609733
DOI: 10.25259/IJDVL_935_2022