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Journal of Cutaneous Pathology Sep 2023
Topics: Humans; Argyria; Elastic Tissue; Ochronosis; Alkaptonuria
PubMed: 37316955
DOI: 10.1111/cup.14476 -
Advances in Clinical Chemistry 2023Alkaptonuria (AKU) is an ultra-rare inherited inborn error of metabolism that afflicts the tyrosine metabolic pathway, resulting in the accumulation of homogentisic acid... (Review)
Review
Alkaptonuria (AKU) is an ultra-rare inherited inborn error of metabolism that afflicts the tyrosine metabolic pathway, resulting in the accumulation of homogentisic acid (HGA) in the circulation, and significant excretion in urine. Clinical manifestations, typically observed from the third decade of life, are lifelong and significantly affect the quality of life. This review provides a comprehensive overview of the natural history of AKU, including clinical, biochemical and genetic perspectives. An update on the major advances on studies in murine models and human subjects, providing mechanistic insight into the molecular and biochemical processes that underlie pathophysiology and its response to treatment are presented. The impact of treatment with nitisinone is also presented with a specific emphasis on hypertyrosinemia, as uncertainty on this topic remains. Future perspectives are explored, such as novel approaches to treat hypertyrosinemia including the use of binding agents and amino acid transporter inhibitors, as well as advanced potentially curative gene and cell therapy initiatives.
Topics: Humans; Animals; Mice; Alkaptonuria; Quality of Life; Tyrosinemias; Homogentisic Acid; Tyrosine
PubMed: 37268334
DOI: 10.1016/bs.acc.2023.02.005 -
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 -
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 -
Cureus Mar 2023Alkaptonuria is a rare genetic metabolic disorder of autosomal recessive inheritance characterised by the accumulation of homogentisic acid in the body. It is diagnosed...
Alkaptonuria is a rare genetic metabolic disorder of autosomal recessive inheritance characterised by the accumulation of homogentisic acid in the body. It is diagnosed upon identification of characteristic symptoms, using various biochemical investigations, radiographic pictures, and a variety of specialised tests. Here we are discussing the case of an 80-year-old female patient with incidental findings of alkaptonuria. It is crucial to understand the fundamental diagnostic investigations that can be used in low-income nations or facilities where investigations like genetic testing, gas chromatography, and mass spectrometry are not readily available for the diagnosis of alkaptonuria.
PubMed: 37025736
DOI: 10.7759/cureus.35792 -
Journal of Orthopaedic Case Reports Nov 2022Ochronosis is a rare metabolic disorder, characterized by accumulation of homogentisic acid in the connective tissues due to the lack of the enzyme homogentisic acid...
INTRODUCTION
Ochronosis is a rare metabolic disorder, characterized by accumulation of homogentisic acid in the connective tissues due to the lack of the enzyme homogentisic acid oxidase. The musculoskeletal manifestation of alkaptonuria is black pigmentation of cartilage of the knee and the hip leading to arthropathy.
CASE REPORT
In this article, we report three patients with involvement of hip, knee, and spine, but with more severe involvement of the hips. Bilateral hip arthroplasty was done in one out of the three patients.
CONCLUSION
Being a rare disorder and often missed, the functional outcome of hip arthroplasty in these patients is similar to primary osteoarthritis. The importance lies in correct diagnosis and anticipation of intraoperative difficulties.
PubMed: 37013237
DOI: 10.13107/jocr.2022.v12.i11.3400 -
Ophthalmic Plastic and Reconstructive...Exogenous ochronosis refers to accumulation of homogentisic acid metabolites in tissues, manifesting as pigmentation of affected tissues. Phenolic compounds are most...
Exogenous ochronosis refers to accumulation of homogentisic acid metabolites in tissues, manifesting as pigmentation of affected tissues. Phenolic compounds are most commonly implicated, including hydroquinone, quinine, phenol, resorcinol, mercury, and picric acid. The affected connective tissues exhibit brownish discoloration when heavily pigmented and the histopathological appearance is characteristic with "banana-shaped" ochre-colored pigment deposits. Herein, the authors describe a rare case of exogenous ochronosis involving the conjunctiva, sclera and skin, as a result of chronic use of Teavigo (94% epigallocatechin gallate), a polyphenol compound with postulated antioxidant and antiapoptotic activity.
Topics: Humans; Ochronosis; Alkaptonuria; Skin; Pigmentation Disorders
PubMed: 37010051
DOI: 10.1097/IOP.0000000000002395 -
Molecules (Basel, Switzerland) Mar 2023Alkaptonuria (AKU) is a rare genetic autosomal recessive disorder characterized by elevated serum levels of homogentisic acid (HGA). In this disease, tyrosine metabolism...
Alkaptonuria (AKU) is a rare genetic autosomal recessive disorder characterized by elevated serum levels of homogentisic acid (HGA). In this disease, tyrosine metabolism is interrupted because of the alterations in homogentisate dioxygenase (HGD) gene. The patient suffers from ochronosis, fractures, and tendon ruptures. To date, no medicine has been approved for the treatment of AKU. However, physiotherapy and strong painkillers are administered to help mitigate the condition. Recently, nitisinone, an FDA-approved drug for type 1 tyrosinemia, has been given to AKU patients in some countries and has shown encouraging results in reducing the disease progression. However, this drug is not the targeted treatment for AKU, and causes keratopathy. Therefore, the foremost aim of this study is the identification of potent and druggable inhibitors of AKU with no or minimal side effects by targeting 4-hydroxyphenylpyruvate dioxygenase. To achieve our goal, we have performed computational modelling using BioSolveIT suit. The library of ligands for molecular docking was acquired by fragment replacement of reference molecules by ReCore. Subsequently, the hits were screened on the basis of estimated affinities, and their pharmacokinetic properties were evaluated using SwissADME. Afterward, the interactions between target and ligands were investigated using Discovery Studio. Ultimately, compounds and were identified as potent inhibitors of 4-hydroxyphenylpyruvate dioxygenase.
Topics: Humans; Alkaptonuria; 4-Hydroxyphenylpyruvate Dioxygenase; Molecular Docking Simulation; Ochronosis; Homogentisic Acid
PubMed: 36985595
DOI: 10.3390/molecules28062623 -
Endocrine Regulations Jan 2023Alkaptonuria (AKU, OMIM, No. 203500) is a rare, slow-progressing, irreversible, multisystemic disease resulting from a deficiency of the homogentisate 1,2-dioxygenase...
Alkaptonuria (AKU, OMIM, No. 203500) is a rare, slow-progressing, irreversible, multisystemic disease resulting from a deficiency of the homogentisate 1,2-dioxygenase enzyme, which leads to the accumulation of homogentisic acid (HGA) and subsequent deposition as pigment in connective tissues called ochronosis. As a result, severe arthropathy of large joints and spondyloarthropathy with frequent fractures, ligament ruptures, and osteoporosis develops in AKU patients. Since 2020, the first-time treatment with nitisinone has become available in the European Union. Nitisinone significantly reduces HGA production and arrests ochronosis in AKU patients. However, blocking of the tyrosine metabolic pathway by the drug leads to tyrosine plasma and tissue concentrations increase. The nitisinone-induced hypertyrosinemia can lead to the development of corneal keratopathy, and once it develops, the treatment needs to be interrupted. A decrease in overall protein intake reduces the risk of the keratopathy during nitisinone-induced hypertyrosinemia in AKU patients. The low-protein diet is not only poorly tolerated by patients, but over longer periods, leads to a severe muscle loss and weight gain due to increased energy intake from carbohydrates and fats. Therefore, the development of novel nutritional approaches is required to prevent the adverse events due to nitisinone-induced hypertyrosinemia and the negative impact on skeletal muscle metabolism in AKU patients.
Topics: Humans; Alkaptonuria; Ochronosis; Tyrosinemias; Tyrosine; Homogentisic Acid
PubMed: 36966367
DOI: 10.2478/enr-2023-0008 -
Journal of Orthopaedic Case Reports Oct 2022Ochronotic arthropathy is a rapidly progressive sequelae of alkaptonuria. This is a rare autosomal recessive condition caused by a mutation in the homogentisate 1,2...
INTRODUCTION
Ochronotic arthropathy is a rapidly progressive sequelae of alkaptonuria. This is a rare autosomal recessive condition caused by a mutation in the homogentisate 1,2 dioxygenase (HGD) gene leading to HGD enzyme deficiency. Here, we report a case of neck femur fracture in a patient with ochronotic arthropathy managed by primary hip arthroplasty.
CASE REPORT
A 62-year-old gentleman presented with complaints of pain in his left groin area and difficulty in weight bearing on his left lower limb for 3 weeks. The pain was sudden in onset and started while he was on his morning walk. He did not have any problems with his left hip before this episode and he did not give a history of any significant trauma. History, radiological, and intraoperative findings revealed ochronotic hip arthropathy.
CONCLUSION
Ochronotic arthropathy is relatively rare and is seen in isolated communities. The treatment options are similar to primary osteoarthritis and the outcome is comparable to arthroplasty done for osteoarthritis.
PubMed: 36874893
DOI: 10.13107/jocr.2022.v12.i10.3346