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Aorta (Stamford, Conn.) Aug 2021A-76-year old male with a past history of alkaptonuria with ochronosis (homogentisic acid deposition in tissues) had symptomatic aortic stenosis. Surgical replacement of...
A-76-year old male with a past history of alkaptonuria with ochronosis (homogentisic acid deposition in tissues) had symptomatic aortic stenosis. Surgical replacement of the valve was undertaken, and he was noted to have a severely pigmented and porcelain aorta.
PubMed: 34715699
DOI: 10.1055/s-0041-1729916 -
British Medical Journal Oct 1952
Topics: Alkaptonuria; Ochronosis; Pigmentation
PubMed: 12978317
DOI: 10.1136/bmj.2.4787.760 -
Journal of Thoracic Disease May 2018Ochronosis is the bluish-black discolouration of connective tissue, including heart valves, joints, kidney and the skin. It is due to the deposition of homogentisic acid...
Ochronosis is the bluish-black discolouration of connective tissue, including heart valves, joints, kidney and the skin. It is due to the deposition of homogentisic acid (HGA) commonly found in alkaptonuria. Ochronosis in the aortic valve is a rare occurrence and there is limited data available on the most appropriate choice of valve prosthesis in these patients. This case involves a 72-year-old male with symptomatic aortic stenosis and on echocardiogram a severe calcific trileaflet aortic stenosis with normal ejection fraction. Intraoperative aortic cannulation was routine and uncomplicated, and bluish-black discolouration of aortic valve was noted. Thorough decalcification was undertaken and a bioprosthetic valve was chosen in accordance with patient's age and preference. There were no complications post-operatively and the patient reported being well. Ochronosis affecting the aortic valve is a rare condition and there is limited data on the recurrence rate as well as the natural history of the disease. This case reports aims to provide data to facilitate further research to better understand the natural history of aortic valve ochronosis and rates of recurrence following bioprosthetic aortic valve replacement (AVR).
PubMed: 29997987
DOI: 10.21037/jtd.2018.05.16 -
BMJ Case Reports Feb 2021Alkaptonuria is a rare genetic disorder resulting in abnormality of tyrosine metabolism. It is one of the Garrod's tetrad of 'inborn errors of metabolism' proposed to...
Alkaptonuria is a rare genetic disorder resulting in abnormality of tyrosine metabolism. It is one of the Garrod's tetrad of 'inborn errors of metabolism' proposed to have Mendelian recessive inheritance. The disorder is characterised by deposition of homogentisic acid leading to ochronosis and ochronotic osteoarthropathy; however, blackish discoloration of urine is the only childhood manifestation. Other manifestations present only after third decade. A 13-year-old boy presented to paediatric nephrology clinic with blackish discolouration of urine since infancy. Examination revealed bluish black discolouration of bilateral sclera and ear cartilage; however, he had no symptoms of ochronotic osteoarthropathy. Genetic test pointed towards alkaptonuria. Currently, he is on regular follow-up and is being treated with vitamin C to delay the progression of the disease. Early diagnosis with appropriate intervention delays the onset of complications and preserves the quality of life of the patient.
Topics: Adolescent; Alkaptonuria; Antioxidants; Ascorbic Acid; Disease Progression; Early Diagnosis; Humans; Male; Ochronosis; Sclera
PubMed: 33541951
DOI: 10.1136/bcr-2020-240147 -
BMC Ophthalmology Jan 2014Ochronosis/Alkaptonuria is a tyrosine metabolism disorder where accumulation of homogentisic acid, in eye, skin, cartilage and several other connective tissues leads to... (Review)
Review
BACKGROUND
Ochronosis/Alkaptonuria is a tyrosine metabolism disorder where accumulation of homogentisic acid, in eye, skin, cartilage and several other connective tissues leads to a black pigmentation of the affected tissues. It is autosomal-recessive inherited in men with a frequency of 1-9/1,000,000. While it is clear that pigment deposits lead to joint destruction, renal stone formation and cardiac valvulopathy respectively, the significance of ocular findings is still unclear. We therefore aim to evaluate the frequency and clinical significance of ocular findings in ochronosis and discuss possible therapeutic options.
METHODS
Systematic review of literature via Medline and Web of Science. Only case reports in English, German, French, Spanish or Italian documenting detailed ophthalmologic examination were included.
RESULTS
Our search revealed 36 case reports including 40 patients. Average age at the onset of ocular signs was 40.6 years. The most frequent sign was symmetric brown sclera pigmentation present in 82.5 percent of the patients. "Oil-drops", brown pigment spots in the limbus are generally considered pathognomonic but were a little less frequent (75 percent). Vermiform pigment deposits at the level of the conjunctiva or increased conjunctival vessel diameter is also frequent. We found an increased incidence of central vein occlusion and elevated intraocular pressure going along with chamber angle hyperpigmentation. Another condition observed twice is rapid progressive astigmatism attributable to corneoscleral pigment accumulation.
CONCLUSION
Our observations suggest that ocular findings are of double relevance. First, characteristic ocular findings can anticipate the time of diagnosis and second, ocular findings may complicate to various conditions putting sight at risk. Opthalmologists and general physicians should be aware of both. Therapeutic options include protein restriction, administration of high dose vitamin C or nitisonone. Evidence for all of them is limited.
Topics: Conjunctival Diseases; Humans; Male; Ochronosis; Scleral Diseases
PubMed: 24479547
DOI: 10.1186/1471-2415-14-12 -
Arthritis 2014This update develops the actual therapeutic options in the management of the joint involvement of calcium pyrophosphate deposition disease (CPPD), basic calcium... (Review)
Review
This update develops the actual therapeutic options in the management of the joint involvement of calcium pyrophosphate deposition disease (CPPD), basic calcium phosphate (BCP) deposition disease, hemochromatosis (HH), ochronosis, oxalosis, and Wilson's disease. Conventional pharmaceutical treatment provides benefits for most diseases. Anti-interleukine-1 (IL-1) treatment could provide similar results in CPPD than in gout flares. There is only limited evidence about the efficacy of preventive long-term colchicine intake, methotrexate, and hydroxychloroquine in chronic CPPD. Needle aspiration and lavage have satisfactory short and midterm results in BCP. Extracorporeal shockwave therapy has also proved its efficacy for high-doses regimes. Phlebotomy does not seem to have shown real efficacy on joint involvement in HH so far. Iron chelators' effects have not been assessed on joint involvement either, while IL-1 blockade may prove useful. NSAIDs have limited efficacy on joint involvement of oxalosis, while colchicine and steroids have not been assessed either. The use of nitisinone for ochronotic arthropathy is still much debated, but it could provide beneficial effects on joint involvement. The effects of copper chelators have not been assessed either in the joint involvement of Wilson's disease. NSAIDs should be avoided because of the liver affection they may worsen.
PubMed: 24895535
DOI: 10.1155/2014/375202 -
Quarterly Bulletin. Northwestern... 1958
Topics: Alkaptonuria; Cortisone; Humans; Ochronosis
PubMed: 13554742
DOI: No ID Found -
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 -
Clinical Medicine & Research Nov 2004Alkaptonuria is a rare autosomal recessive disorder of metabolism caused by deficiency of homogentisic acid oxidase and resulting in accumulation of homogentisic acid in... (Review)
Review
Alkaptonuria is a rare autosomal recessive disorder of metabolism caused by deficiency of homogentisic acid oxidase and resulting in accumulation of homogentisic acid in collagenous structures. It is characterized by homogentisic aciduria, bluish-black discoloration of connective tissues (ochronosis) and arthropathy of large joints. Less common manifestations include cardiovascular abnormalities, renal, urethral and prostate calculi. Bone fractures are unusual in ochronosis. In this report, we describe a woman, 69 years of age, with a history of dark urine since childhood and progressive pigmentation of the skin, sclera, and auricular cartilages. She had severe arthropathy requiring total joint replacement in both of her knees and right hip. She also had severe aortic stenosis requiring valve replacement, and asymptomatic nephrolithiasis. She presented with a low trauma fracture of the distal femur despite two years of alendroate therapy. We review the etiology, pathogenesis, clinical presentation, diagnosis and treatment of alkaptonuric ochronosis. Early detection is important for prevention and treatment of multiple systems. Nitisinone, a potent inhibitor of 4-hydroxyphenylpyruvate dioxygenase, dramatically reduces production and urinary excretion of homogentisic acid; however, the long-term efficacy and side effects of such therapy are unknown. Identifying the gene for alkaptonuria offers the potential for a new therapeutic approach (replacement therapy with a recombinant enzyme) in the treatment of alkaptonuric ochronosis.
Topics: Aged; Alkaptonuria; Aortic Valve Insufficiency; Female; Femoral Fractures; Heart Valve Prosthesis; Humans; Internal Fixators; Ochronosis
PubMed: 15931360
DOI: 10.3121/cmr.2.4.209 -
JPRAS Open Dec 2021Ochronosis is a syndrome characterized by bluish black discoloration due to the deposition of polymerized products of homogentisic acid (HGA) in the connective tissues....
Ochronosis is a syndrome characterized by bluish black discoloration due to the deposition of polymerized products of homogentisic acid (HGA) in the connective tissues. The endogenous variety (alkaptonuria), is a rare autosomal recessive metabolic disorder. The disorder is manifested by deficiency of the enzyme homogentisate 1,2-dioxygenase. The characteristic of the condition is a triad of pigmentation of skin, cartilage, and sclera; ochronotic arthropathies and homogentisic aciduria (resulting in darkening of urine). More rarely, it may affect the breast. This rare and interesting case of a woman with ochronosis of both breasts and chest wall, prompted us to write this case report.
PubMed: 34381863
DOI: 10.1016/j.jpra.2021.06.005