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Dermatology Online Journal Apr 2019Endogenous ochronosis (EO) or alkaptonuria is an inherited autosomal recessive disease caused by the insufficiency of the enzyme homogentisic acid dioxygenase. This...
Endogenous ochronosis (EO) or alkaptonuria is an inherited autosomal recessive disease caused by the insufficiency of the enzyme homogentisic acid dioxygenase. This disturbance causes an accumulation and increased renal excretion of homogentisic acid (AHG), which manifests as dark urine when it oxidizes on contact with air. Other clinical manifestations of OE are the result of the deposit of AHG in the form of ochronotic pigment at the level of collagen in the skin and cartilage, where it causes blue-gray cutaneous hyperpigmentation, degenerative arthropathy, valvular disease, and other multisystem effects. Despite the progressive and irreversible nature of OE and the lack of a curative treatment, the life expectancy is preserved. We report a new case of EO with cutaneous and joint involvement, in which a high clinical suspicion, confirmed by elevated AHG in urine was the key in the diagnosis.
Topics: Alkaptonuria; Female; Homogentisic Acid; Humans; Hyperpigmentation; Joint Diseases; Middle Aged; Ochronosis
PubMed: 31046911
DOI: No ID Found -
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 -
Journal of Clinical Medicine Research May 2019Alkaptonuria (AKU) is a rare genetic disease associated with the deposition of melanin-like pigments (ochronosis) in connective tissues. However, data regarding the...
BACKGROUND
Alkaptonuria (AKU) is a rare genetic disease associated with the deposition of melanin-like pigments (ochronosis) in connective tissues. However, data regarding the effect of oxidative stress products on disease pathogenesis are limited. The purpose of this study was to investigate oxidative stress and related factors in patients with alkaptonuria and compare the findings with those in healthy control subjects.
METHODS
The study sample comprised of 21 AKU patients and 19 age- and sex-matched healthy controls. Serum samples were obtained to detect the total antioxidative capacity (TAC), and oxidation degradation products of thiobarbituric acid-reactive substances, protein carbonyls, advanced oxidation protein products, and homogentisic acid levels in urine were determined.
RESULTS
Serum TAC, oxidation degradation products of thiobarbituric acid-reactive substances, and protein carbonyl levels in the AKU group were higher than those measured for the control subjects, and the difference was statistically significant (P < 0.05). Moreover, a positive correlation was found between the patient's serum protein carbonyl, patient's age and AKU severity score (r = 0.492 and 0.746, respectively; P < 0.05). Furthermore, the protein carbonyl serum levels can be used to predict the disease severity score in alkaptonuria patients (P < 0.05).
CONCLUSIONS
In sum, the study results provide further support for the role of oxidation in the pathogenesis of alkaptonuria, suggesting presence of a more complex relationship than what has been previously assumed. Thus, further studies are needed to clarify these conflicting results.
PubMed: 31019628
DOI: 10.14740/jocmr3801 -
Annals of Dermatology Feb 2019
PubMed: 33911553
DOI: 10.5021/ad.2019.31.1.106 -
Journal of Orthopaedic Case Reports 2018Ochronosis is an inherited metabolic disease that causes a brownish-black pigmentation of the connective tissue. There is currently no specific treatment for ochronosis....
INTRODUCTION
Ochronosis is an inherited metabolic disease that causes a brownish-black pigmentation of the connective tissue. There is currently no specific treatment for ochronosis. The goal of treatment is to control the progress of disease with a multidisciplinary approach and symptomatic relief. Arthroplasty in ochronotic arthropathy patients has shown good to excellent results comparable to arthroplasty performed in patients with degenerative osteoarthritis.
CASE REPORT
We report an unusual case of a 69-year-old female who suffered advanced degenerative arthropathy secondary to ochronosis. A staged bilateral total hip arthroplasty was performed on her successfully using a Corail metal on poly total hip prosthesis 9months apart.
CONCLUSION
Ochronoticarthropathy produces degenerative arthritis of large joints in middle-aged patients. In many cases, the patient does not know the disease until the diagnosis of intraoperative suspicion. There is no definitive treatment. After conservative management, joint replacement surgery offers the best symptomatic treatment.
PubMed: 30687653
DOI: 10.13107/jocr.2250-0685.1136 -
The Archives of Bone and Joint Surgery Nov 2018Ochronosis or black joints disorder is a rare autosomal recessive disorder caused by deficiency of homogentisic acid oxidase. Orthopaedic manifestations are common and...
Ochronosis or black joints disorder is a rare autosomal recessive disorder caused by deficiency of homogentisic acid oxidase. Orthopaedic manifestations are common and mostly involve spine and large joints such as knee and hip. Arthropathy is progressive and will eventually leads to arthroplasty. Not being familiar with this disorder might lead to devastating complications. We present a 57 year-old woman with Ochronosis who successfully underwent cemented cruciated substituted knee replacement and cementless hip replacement. Proper orthopaedic and anesthetic pre-operative preparation, soft tissue specially patella tendon management throughout operation and meticulous bleeding control during surgery are crucial. The results of the knee and the hip replacement surgery in this patient are satisfactory, after 24 months and 18 months follow-up, respectively. If Orthopaedic surgeons and anesthesiologists are well prepared, the outcome of joint replacement in Ochronosis patients will be as satisfactory as patients with primary osteoarthritis.
PubMed: 30637315
DOI: No ID Found -
Arthroscopy Techniques Nov 2018The surgical treatment of ochronotic arthropathy remains unclear. Although there is no absolute cure for ochronotic arthropathy, current management typically begins with...
The surgical treatment of ochronotic arthropathy remains unclear. Although there is no absolute cure for ochronotic arthropathy, current management typically begins with conservative treatment. Total joint replacement may eventually be necessary for joints that become severely degenerative. Ochronotic arthropathy is present in patients with alkaptonuric ochronosis, which is characterized by dark pigmentation of connective tissue and black discoloration of urine owing to a deficiency of homogentisic acid oxidase. As a result, soft tissues become brittle and subsequently more susceptible to mechanical stress, resulting in articular cartilage degeneration. The diagnosis of ochronotic arthropathy of the knee often occurs intraoperatively after discovery of darkened synovium and black deposits during arthroscopy. The purpose of this article is to describe arthroscopic debridement as an effective treatment option and diagnostic tool for ochronotic arthropathy of the knee after failure of conservative measures.
PubMed: 30533354
DOI: 10.1016/j.eats.2018.07.004 -
Medical Journal, Armed Forces India Oct 2018
PubMed: 30449931
DOI: 10.1016/j.mjafi.2017.06.006 -
Revista Da Associacao Medica Brasileira... Jul 2018
Topics: Alkaptonuria; Female; Humans; Middle Aged; Ochronosis; Osteoarthritis
PubMed: 30365658
DOI: 10.1590/1806-9282.64.07.583 -
Data in Brief Oct 2018Alkaptonuria is a rare genetic disorder characterized by a high level of circulating (and urine) homogentisic acid (HGA), which contributes to ochronosis when it is...
Alkaptonuria is a rare genetic disorder characterized by a high level of circulating (and urine) homogentisic acid (HGA), which contributes to ochronosis when it is deposited in connective tissue as a pigmented polymer. In an observational study carried out by National AKU Centre (NAC) in Liverpool, a total of thirty-nine AKU patients attended yearly visits in varying numbers. At each visit a mixture of clinical, joint and spinal assessments were carried out and the results calculated to yield an AKUSSI (Alkaptonuria Severity Score Index), see "Nitisinone arrests ochronosis and decreases rate of progression of Alkaptonuria: evaluation of the effect of nitisinone in the United Kingdom National Alkaptonuria Centre" (Ranganath at el., 2018). The aim of this data article is to produce visual representation of the change in the components of AKUSSI over 3 years, through radar charts. The metabolic effect of nitisinone is shown through box plots.
PubMed: 30263914
DOI: 10.1016/j.dib.2018.09.021