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Annals of Medicine and Surgery (2012) May 2024Alkaptonuria is an autosomal extremely rare recessive metabolic disorder with incidence reported to occur as 1:100 000-1:250 000 live births worldwide. This rare...
INTRODUCTION
Alkaptonuria is an autosomal extremely rare recessive metabolic disorder with incidence reported to occur as 1:100 000-1:250 000 live births worldwide. This rare metabolic disorder is characterized by the accumulation of homogentisic acid due to a deficiency in homogentisic acid 1,2 dioxygenase. Homogentisic acid subsequently oxidizes and accumulates in the connective tissue. The knee is the most significant peripheral joint to be affected by the disorder. The authors present the first case of ochronotic arthropathy in Syria.
CASE PRESENTATION
A 46-year-old male presented with bilateral pain in the knees. the pain was affecting his day-to-day activities, and not responding to conservative management. Anteroposterior standing radiographs demonstrated extensive degenerative disease. Intraoperatively, the diagnosis was done after noticing that the quadriceps tendon and the articular cartilage of the femur, tibia, and patella were blackened during cemented total knee replacement of the knee.
CONCLUSION
Ochronotic arthropathy should be kept in mind in middle age patients with severe osteoarthritis to not be surprised by the rare alkaptonuria diagnosis if arthroplasty was indicated.
PubMed: 38694340
DOI: 10.1097/MS9.0000000000001775 -
Journal of Orthopaedic Case Reports Feb 2024Alkaptonuria is a rare autosomal recessive disorder caused by the defective metabolism of homogentisic acid, with a rare course and remained undetected even until...
INTRODUCTION
Alkaptonuria is a rare autosomal recessive disorder caused by the defective metabolism of homogentisic acid, with a rare course and remained undetected even until adulthood. Ochronotic arthropathy is one of the manifestations of alkaptonuria, predominantly affecting weight bearing joints such as spine, hip, and knee. Total joint arthroplasty is treatment of choice in end-stage arthritis of hip and knee. Owing to the rarity of the disease, limited data is available in literature regarding surgical challenges and long-term functional outcomes.
CASE REPORT
Herein, we present a case of 43-year-old male with ochronotic arthropathy of bilateral hip, right knee, and bilateral elbow joints with involvement of spine, who was incidentally diagnosed with ochronotic arthropathy intraoperatively and underwent sequential arthroplasty for right hip followed by right knee and left hip over a period of 10 years. At 11 years' follow-up, the patient has full mobility with no loosening of implants.
CONCLUSION
The long-term results of total joint arthroplasty in ochronotic arthropathy are good. Surgeon should be aware of the difficulty in soft tissue balancing and possible complications in the ochronotic arthropathy and require a conscientious approach to avoid complications.
PubMed: 38420236
DOI: 10.13107/jocr.2024.v14.i02.4224 -
European Heart Journal. Case Reports Feb 2024Alkaptonuria is a rare metabolic disease that causes an increase in homogentisic acid (HGA) due to a lack of enzymatic activity. Commonly, accumulation of HGA presents...
BACKGROUND
Alkaptonuria is a rare metabolic disease that causes an increase in homogentisic acid (HGA) due to a lack of enzymatic activity. Commonly, accumulation of HGA presents with dark discoloration of skin and other tissues, also known as ochronosis. Additionally, alkaptonuria can result in other clinical manifestations, including arthritis and cardiac disease. This case highlights alkaptonuria-related cardiac disease and challenges that cardiac surgery teams may face when treating this patient population.
CASE SUMMARY
A 62-year-old male with a history of alkaptonuria, Hodgkin's lymphoma treated with chemoradiation, hypertension, and hyperlipidaemia originally presented with shortness of breath in the setting of known cardiac disease. Cardiac work-up demonstrated aortic stenosis, mitral stenosis, and multivessel coronary artery disease requiring aortic valve replacement, mitral valve replacement, and coronary artery bypass grafting. During the operation, significant discoloration of tissue was observed. This correlated with areas of severe calcification, which was noted throughout both valves. Extensive debridement was required prior to proceeding to valve replacements. Additionally, near-infrared spectroscopy failed to provide accurate measurements of cerebral oxygenation.
DISCUSSION
Alkaptonuria is correlated with cardiovascular disease, particularly valvular disease. Intraoperatively, these patients may exhibit noticeable discoloration and severe calcification of various tissues. Additionally, traditional infrared-based methods of cerebral oxygenation monitoring may not be reliable; however, other options of cerebral monitoring may be feasible. With proper pre-operative planning, however, patients with alkaptonuria may safely undergo cardiac surgery.
PubMed: 38405194
DOI: 10.1093/ehjcr/ytae076 -
Journal of Orthopaedic Case Reports Dec 2023Alkaptonuria (AKU) is a rare autosomal-recessive multisystemic disease. It is caused by a mutant homogentisate dioxygenase coding gene, leading to the accumulation of...
INTRODUCTION
Alkaptonuria (AKU) is a rare autosomal-recessive multisystemic disease. It is caused by a mutant homogentisate dioxygenase coding gene, leading to the accumulation of homogentisic acid (HGA), hence systemic manifestations. Renal manifestations and tendon rupture are rarely reported.
CASE REPORT
We report a 60-year-old male with chronic kidney disease for over a decade who was initially misdiagnosed with ankylosing spondylitis and rheumatoid arthritis. Later on, the patient presented to our institute with a non-synchronized (8 years) acute quadriceps tendon rupture.
CONCLUSION
Physicians should be aware of the importance of prophylactic measures in the management of AKU, which is mainly medical management, to reduce the accumulation of HGA in the body. We further emphasize this point to reduce the incidence of subsequent tendon ruptures, as it significantly affects the quality of life.
PubMed: 38162369
DOI: 10.13107/jocr.2023.v13.i12.4088 -
Cureus Oct 2023Alkaptonuria is a rare genetic disorder characterized by the excessive production of homogentisic acid, leading to the formation and deposition of pigment polymers...
Alkaptonuria is a rare genetic disorder characterized by the excessive production of homogentisic acid, leading to the formation and deposition of pigment polymers throughout the body. It is extremely rare, affecting only around one in 100,000 individuals. Despite the normal life expectancy, it can cause severe morbidities. Alkaptonuria is typically managed supportively with pain medication, dietary modifications, and surgical interventions, which are considered to be the gold standard of therapy. Here we present a case of a 33-year-old male with no previous medical or surgical history who presented with severe acute back pain radiating to the left leg. Genetic testing confirmed a homozygous pathogenic variant for alkaptonuria. This case highlights the challenges in diagnosing alkaptonuria, emphasizing the significance of early detection, and clinical evaluation for improved outcomes. Furthermore, it underscores the need to consider alkaptonuria as a multidimensional disease, necessitating further research to enhance our understanding and develop effective management. Therefore, this study serves as an opportunity for future trials and studies aimed at digging deeper into the intricacies of alkaptonuria to increase our understanding and establish comprehensive management plans for affected individuals.
PubMed: 37937039
DOI: 10.7759/cureus.46644 -
Biomedicines Sep 2023Endogenous ochronosis, also known as alkaptonuria, is a rare disease known for its bluish-black discoloration of the skin, sclerae, and pinnae, as well as urine that...
Endogenous ochronosis, also known as alkaptonuria, is a rare disease known for its bluish-black discoloration of the skin, sclerae, and pinnae, as well as urine that turns black upon standing. Though rarely fatal, joint degradation is a common sequela, and many patients require multiple large joint arthroplasties throughout their lifetime. Though many aspects of the pathophysiological mechanisms of the disease have been described, questions remain, such as how the initiation of ochronotic pigmentation is prompted and the specific circumstances that make some tissues more resistant to pigmentation-related damage than others. In this report, we present the case of an 83-year-old female previously diagnosed with alkaptonuria including high-quality arthroscopic images displaying the fraying of articular cartilage. We also offer a summary of the latest literature on the pathophysiological mechanisms of the disease, including cellular-level changes observed in ochronotic chondrocytes, biochemical and mechanical alterations to the cartilaginous extracellular matrix, and patterns of pigmentation and joint degradation observed in humans and mice models. With these, we present an overview of the mechanisms of ochronotic chondropathy and joint degradation as the processes are currently understood. While alkaptonuria itself is rare, it has been termed a "fundamental disease," implying that its study and greater understanding have the potential to lead to insights in skeletal biology in general, as well as more common pathologies such as osteoarthritis and their potential treatment mechanisms.
PubMed: 37892999
DOI: 10.3390/biomedicines11102625 -
Journal of Clinical Laboratory Analysis Nov 2023Homogentisic acid (HGA) is excreted in excessive amounts in the urine of patients with alkaptonuria, which is a hereditary metabolic disorder of phenylalanine and...
OBJECTIVE
Homogentisic acid (HGA) is excreted in excessive amounts in the urine of patients with alkaptonuria, which is a hereditary metabolic disorder of phenylalanine and tyrosine. Therefore, the detection of HGA in urine is useful for the diagnosis of alkaptonuria. To evaluate the detection of HGA, we confirmed the color shift of HGA solutions and analyzed them by electrospray ionization mass spectrometry (ESI-MS).
METHODS
We observed the color change of the HGA solutions under different pH conditions (pH 6.0, 7.0, and 8.0) and examined the influences of adding potassium hydroxide (KOH) and ascorbic acid (AA) to the HGA solutions. Then, we analyzed the chemical reaction in HGA solutions using ESI-MS.
RESULTS
The HGA solution at pH 8.0 became brown after incubation at room temperature for 24 h and became darker brown with the addition of KOH; however, HGA solutions at pH 6.0 and 7.0 showed no color changes. The brown color change of the HGA solution at pH 8.0 was also inhibited by AA. Moreover, all HGA sample solutions showed the deprotonated molecular ion peak at m/z 167.035 in the negative ion mode after incubation at room temperature for 24 h and with the addition of KOH and AA.
CONCLUSION
We identified the molecular ion of HGA in all sample solutions by ESI-MS, regardless of different pH conditions, color changes, or the presence of AA. These results suggest that spectral analysis by ESI-MS is suitable for the detection of HGA and the diagnosis of alkaptonuria.
Topics: Humans; Alkaptonuria; Spectrometry, Mass, Electrospray Ionization; Homogentisic Acid; Hydroxides; Ascorbic Acid
PubMed: 37877521
DOI: 10.1002/jcla.24976 -
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 -
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 -
Journal of Bone Metabolism Aug 2023Alkaptonuria is an extremely rare autosomal recessive metabolic disorder characterized by dark urine, ochronosis, and arthritis of the spine and major joints. We report...
Alkaptonuria is an extremely rare autosomal recessive metabolic disorder characterized by dark urine, ochronosis, and arthritis of the spine and major joints. We report a case of ochronotic arthritis observed during total knee replacement surgery in a 65-year-old male patient with no relevant medical history. Based on a literature review, this is the first case of ochronotic arthritis reported in Korea.
PubMed: 37718906
DOI: 10.11005/jbm.2023.30.3.283