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Dermatology Online Journal Nov 2010A 69-year-old woman presented with a 30-year history of lower back and large joint pain of the hips and shoulders. On examination blue-grey, pigmented macules were...
A 69-year-old woman presented with a 30-year history of lower back and large joint pain of the hips and shoulders. On examination blue-grey, pigmented macules were present over the cartilaginous portions of the ears and on the sclera. Past medical history included aortic stenosis. Urine homogentisic acid level was elevated, which is diagnostic for alkaptonuria. Alkaptonuria is an autosomal recessive disorder that results in deficiency of homogentisic acid oxidase and in the accumulation of homogentisic acid in connective tissue. Disease can result in blue-grey pigmentation of the cartilage, sclerae, face, and hands as well as severe arthropathy and cardiac valve disease. Treatment is limited at this time. Promising early reports of the use of nitisinone have prompted ongoing trials of this therapeutic agent.
Topics: Aged; Alkaptonuria; Arthritis; Cyclohexanones; Female; Homogentisic Acid; Humans; Joint Diseases; Nitrobenzoates; Ochronosis; Pigmentation Disorders
PubMed: 21163157
DOI: No ID Found -
Indian Journal of Dermatology Mar 2011A case of alkaptonuria, a rare disorder with autosomal recessive inheritance, is reported here. The patient had palmar pigmentation in addition to the usual features of...
A case of alkaptonuria, a rare disorder with autosomal recessive inheritance, is reported here. The patient had palmar pigmentation in addition to the usual features of alkaptonuria.
PubMed: 21716546
DOI: 10.4103/0019-5154.80415 -
Calcified Tissue International Sep 2021Osteoarthritis (OA) is one of the most prevalent conditions in the world, particularly in the developed world with a significant increase in cases and their predicted... (Review)
Review
Osteoarthritis (OA) is one of the most prevalent conditions in the world, particularly in the developed world with a significant increase in cases and their predicted impact as we move through the twenty-first century and this will be exacerbated by the covid pandemic. The degeneration of cartilage and bone as part of this condition is becoming better understood but there are still significant challenges in painting a complete picture to recognise all aspects of the condition and what treatment(s) are most appropriate in individual causes. OA encompasses many different types and this causes some of the challenges in fully understanding the condition. There have been examples through history where much has been learnt about common disease(s) from the study of rare or extreme phenotypes, particularly where Mendelian disorders are involved. The often early onset of symptoms combined with the rapid and aggressive pathogenesis of these diseases and their predictable outcomes give an often-under-explored resource. It is these "rarer forms of disease" that William Harvey referred to that offer novel insights into more common conditions through their more extreme presentations. In the case of OA, GWAS analyses demonstrate the multiple genes that are implicated in OA in the general population. In some of these rarer forms, single defective genes are responsible. The extreme phenotypes seen in conditions such as Camptodactyly Arthropathy-Coxa Vara-pericarditis Syndrome, Chondrodysplasias and Alkaptonuria all present potential opportunities for greater understanding of disease pathogenesis, novel therapeutic interventions and diagnostic imaging. This review examines some of the rarer presenting forms of OA and linked conditions, some of the novel discoveries made whilst studying them, and findings on imaging and treatment strategies.
Topics: COVID-19; Coxa Vara; Humans; Osteoarthritis; SARS-CoV-2; Synovitis
PubMed: 34417863
DOI: 10.1007/s00223-021-00896-3 -
Acta Bio-medica : Atenei Parmensis Jun 2022Alkaptonuria is a rare disease characterized by the accumulation of homogentisic acid (HGA). Over time, these patients may develop disabling ochronotic arthropathy. We...
BACKGROUND AND OBJECTIVE
Alkaptonuria is a rare disease characterized by the accumulation of homogentisic acid (HGA). Over time, these patients may develop disabling ochronotic arthropathy. We present 2 cases of patients with end-stage arthropathy treated with total knee arthroplasty (TKA).
METHODS
Both patients complained of disabling knee pain and reported limited walking distance (200-300 m). One had a history of osteotomy for medial knee arthtritis and ignored his underlying condition. The other presented with valgus gonoarthrosis and diagnosis of alkaptonuria.
RESULTS
Intraoperatively, the characteristic dark-blue color in the joint was observed. Both patients evolved favorably after TKA with excellent results according to the Knee Society Scores (KSS) at three years of follow-up.
CONCLUSION
We believe TKA is the right treatment for patients with end-stage disease because it offers considerable relief from pain and allows patients to recover function.
Topics: Alkaptonuria; Arthroplasty, Replacement, Knee; Humans; Joint Diseases; Ochronosis; Pain
PubMed: 35671127
DOI: 10.23750/abm.v92iS1.10439 -
The Hospital May 1899
PubMed: 29820037
DOI: No ID Found -
Metabolites Jan 2019Sir Archibald Edward Garrod, who pioneered the field of inborn errors of metabolism and first elucidated the biochemical basis of alkaptonuria over 100 years ago,... (Review)
Review
Sir Archibald Edward Garrod, who pioneered the field of inborn errors of metabolism and first elucidated the biochemical basis of alkaptonuria over 100 years ago, suggested that inborn errors of metabolism were "merely extreme examples of variations of chemical behavior which are probably everywhere present in minor degrees, just as no two individuals of a species are absolutely identical in bodily structure neither are their chemical processes carried out on exactly the same lines", and that this "chemical individuality [confers] predisposition to and immunities from various mishaps which are spoken of as diseases". Indeed, with advances in analytical biochemistry, especially the development of metabolomics in the post-genomic era, emerging data have been demonstrating that the levels of many metabolites do show substantial interindividual variation, and some of which are likely to be associated with common diseases, such as osteoarthritis (OA). Much work has been reported in the literature on the metabolomics of OA in recent years. In this narrative review, we provided an overview of the identified alteration of metabolic pathways in OA and discussed the role of those identified metabolites and related pathways in OA diagnosis, prognosis, and treatment.
PubMed: 30634493
DOI: 10.3390/metabo9010011 -
Clinical Medicine Insights. Arthritis... 2023Ankylosing spondylitis is the most common type of seronegative inflammatory spondyloarthropathy often presenting with low back or neck pain, stiffness, kyphosis and... (Review)
Review
Ankylosing spondylitis is the most common type of seronegative inflammatory spondyloarthropathy often presenting with low back or neck pain, stiffness, kyphosis and fractures that are initially missed on presentation; however, there are other spondyloarthropathies that may present similarly making it a challenge to establish the correct diagnosis. Here, we will highlight the similarities and unique features of the epidemiology, pathophysiology, presentation, radiographic findings, and management of seronegative inflammatory and metabolic spondyloarthropathies as they affect the axial skeleton and mimic ankylosing spondylitis. Seronegative inflammatory spondyloarthropathies such as psoriatic arthritis, reactive arthritis, noninflammatory spondyloarthropathies such as diffuse idiopathic skeletal hyperostosis, and ochronotic arthritis resulting from alkaptonuria can affect the axial skeleton and present with symptoms similar those of ankylosing spondylitis. These similarities can create a challenge for providers as they attempt to identify a patient's condition. However, there are characteristic radiographic findings and laboratory tests that may help in the differential diagnosis. Axial presentations of seronegative inflammatory, non-inflammatory, and metabolic spondyloarthropathies occur more often than previously thought. Identification of their associated symptoms and radiographic findings are imperative to effectively diagnose and properly manage patients with these diseases.
PubMed: 37533960
DOI: 10.1177/11795441231186822 -
American Journal of Human Genetics Sep 1998
Topics: 4-Hydroxyphenylpyruvate Dioxygenase; Alkaptonuria; Amino Acid Metabolism, Inborn Errors; Cyclohexanones; Enzyme Inhibitors; Humans; Nitrobenzoates; Tyrosine
PubMed: 9718357
DOI: 10.1086/302027 -
International Journal of Surgery Case... Nov 2022Alkaptonuria is an autosomal recessive disease due to lack of the enzyme homogentisic acid oxidase. Homogentisic Acid (HA) is in the metabolism pathway of phenylalanine....
INTRODUCTION AND IMPORTANCE
Alkaptonuria is an autosomal recessive disease due to lack of the enzyme homogentisic acid oxidase. Homogentisic Acid (HA) is in the metabolism pathway of phenylalanine. The musculoskeletal symptomatology begins generally in the fourth decade. We reported the case of a 50 year old man who had ochronotic arthropathy and degenerative changes in knee joint and who was treated with total knee arthroplasty.
CASE PRESENTATION
A 50 year old man presented to our outpatient clinic with bilateral knee pain. Pain was exaggerated with effort and decreases with rest. The patient had no medical history. While performing the total knee arhtroplasty for our patient, we discovered intraoperatively the black coloration of the articular cartilage of the knee. At 6 months follow up, the patient was satisfied with the result with no knee pain in the treated knee. Range of knee motion was 0° in total extension to 100° of flexion. Radiological control showed a stable prosthesis not affected by ochronose.
CLINICAL DISCUSSION
Alkaptonuria is caused by lack of the enzyme homogentisic acid oxidase, is a rare autosomal recessive disease leading accumulation of homogentisic acid in connective tissue. This leads to many manifestations such as urinary, cardiac, dermatologic, ophthalmologic or musculoskeletal symptoms. Deposit of Homogentisic acid in articular cartilage gives the characteristic black or dark brown pigmentation of the cartilage. Its clinical traduction is symptomatology of degenerative modifications in multiples joints such as knee, shoulder or hip beside the lumbar spine arthrosis.
CONCLUSION
Alkapyonuria is a very rare condition. Revealed by its orthopedic features is exceptionally. The patients, generally, need articulations replacement and the illness have no effect on its prognosis.
PubMed: 36327861
DOI: 10.1016/j.ijscr.2022.107682