1,013 results match your criteria Ochronosis


Evaluating the aortic stenosis phenotype before and after the effect of homogentisic acid lowering therapy: Analysis of a large cohort of eighty-one alkaptonuria patients.

Mol Genet Metab 2021 May 21. Epub 2021 May 21.

Department of Cardiology(,) Royal Liverpool University Hospital, Prescot Street, Liverpool, L7 8XP, UK.

Aims: A large alkaptonuria (AKU) cohort was studied to better characterise the poorly understood phenotype of aortic stenosis of rare disease AKU.

Methods And Results: Eighty-one patients attended the National Alkaptonuria Centre (NAC) between 2007 and 2020. Nine only attended once. Read More

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Exogenous ochronosis associated with dimethoxytolyl propylresorcinol (UP302).

J Dermatol 2021 May 25. Epub 2021 May 25.

Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.

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A case report of pregnancy in untreated alkaptonuria - Focus on urinary tissue remodelling markers.

Mol Genet Metab Rep 2021 Jun 29;27:100766. Epub 2021 Apr 29.

Nordic Bioscience, Herlev, Denmark.

A 34-year old woman with alkaptonuria had an elective pregnancy, during which she collected urine samples over the duration of her pregnancy until parturition. She had been attending the National Alkaptonuria Centre from the age of 31 years and continued to attend after delivery for a further three annual visits. Data from her NAC visits as well as urine samples collected during pregnancy were analysed. Read More

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Dermatoscopic Features of Pigmentary Diseases in Ethnic Skin.

Indian Dermatol Online J 2021 Jan-Feb;12(1):24-33. Epub 2021 Jan 16.

Department of Dermatology, S Nijalingappa Medical College, Bagalkot, Karnataka, India.

Dermatoscopy is a non-invasive, handy tool, which is increasingly being used in diagnosis and prognostication of pigmentary dermatoses. Dermatoscopic changes in pigmentary pattern, scaling, and vasculature help us to differentiate among the myriad of hypo and hyper pigmentary diseases. This review gives a brief overview of the dermatoscopic features of pigmentary diseases, which are commonly encountered in clinical practice. Read More

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January 2021

Alkaptonuria in Turkey: Clinical and molecular characteristics of 66 patients.

Eur J Med Genet 2021 May 18;64(5):104197. Epub 2021 Mar 18.

Department of Pediatric Metabolism and Nutrition, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey; Izmir Biomedicine and Genome Center, Izmir, Turkey. Electronic address:

Alkaptonuria (AKU) is an inborn error of metabolism caused by the deficiency of homogentisate 1,2-dioxygenase (HGD) as a result of a defect in the HGD gene. HGD enzyme deficiency results in accumulation of homogentisic acid (HGA) in the body, which in turn leads to multisystemic clinical symptoms. The present study aimed to investigate the presenting symptoms, age at diagnosis, and clinical and genetic characteristics of AKU patients followed-up in different centers in Turkey. Read More

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Intraoperative Diagnosis of a Rare Case of Arthropathy - A Case Report and Review of Literature.

J Orthop Case Rep 2020 Nov;10(8):58-62

Department of Orthopaedics, Seth Gordhandas Sunderdas Medical College and King Edward Memorial Hospital, Mumbai. Maharashtra, India.

Introduction: Alkaptonuria is a rare metabolic disorder of autosomal recessive pattern of inheritance caused due to homogentisic acid oxidase enzyme deficiency. As a result, polymers of homogentisic acid get deposited in excessive amounts in the connective tissues, leading to brownish-black pigmentation termed as ochronosis. As the disease progresses, chronic inflammation results in arthritis of large weight-bearing joints. Read More

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November 2020

A Mimic of Ankylosing Spondylitis, Ochronosis: Case Report and Review of the Literature.

Curr Allergy Asthma Rep 2021 Mar 5;21(3):19. Epub 2021 Mar 5.

Division of Rheumatology and Immunology, Department of Medicine, Duke University, Durham, NC, 27710, USA.

Purpose Of Review: Ochronosis and alkaptonuria are manifestations of the same condition-a rare autosomal recessive disorder resulting from a constitutional lack of homogentisate 1,2-dioxygenase (HGD) with the consequent accumulation of homogentisic acid (HGA). In ochronosis, HGA undergoes autoxidation as well as enzymatic oxidation to form an ochronotic pigment that accumulates in cartilage and connective tissues. In the beginning, there is homogentisic aciduria and pigmentation of cartilages and other connective tissues. Read More

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Occupational Localized Cutaneous Argyria With Pseudo-Ochronosis in a Jeweler.

Am J Dermatopathol 2021 Feb 16. Epub 2021 Feb 16.

Department of Dermatology, Chelsea and Westminster Hospital, London, United Kingdom; Department of Histopathology, Royal Hallamshire Hospital, Sheffield, United Kingdom; Biomedical Imaging Unit, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom; Department of Plastic and Reconstructive Surgery, Chelsea and Westminster Hospital, London, United Kingdom; and Department of Dermatopathology, St George's University Hospital, London, United Kingdom.

Abstract: A case of localized argyria in a 36-year-old female jeweler is described who presented with 2 discrete and asymptomatic bluish-black pigmented macules on the pulp of her left middle finger. A skin biopsy from both lesions demonstrated deposition of brown/black pigmented granules along the basement membrane zone of eccrine glands, blood vessels, nerves, and the dermo-epidermal junction fully in keeping with silver deposition. In addition, there was yellow-brown deposition seen within the interstitial dermis mimicking an early form of ochronosis, so called "pseudo-ochronosis. Read More

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February 2021

Cervical Spondylotic Myelopathy Secondary to Ochronotic Vertebral Arthropathy.

Neurology 2021 03 10;96(13):627-628. Epub 2021 Feb 10.

From the Division of Neuromuscular Diseases, Department of Neurology and Neurosurgery, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.

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Alkaptonuria in an adolescent boy.

BMJ Case Rep 2021 Feb 4;14(2). Epub 2021 Feb 4.

MBBS, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India.

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. Read More

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February 2021

Ochronosis.

N Engl J Med 2021 Feb 30;384(5):461. Epub 2021 Jan 30.

Humanitas Clinical and Research Center, IRCCS, Rozzano, Italy

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February 2021

Perforating and granulomatous exogenous ochronosis.

J Cutan Pathol 2021 Jan 20. Epub 2021 Jan 20.

Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.

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January 2021

Homogentisic acid induces cytoskeleton and extracellular matrix alteration in alkaptonuric cartilage.

J Cell Physiol 2021 Aug 20;236(8):6011-6024. Epub 2021 Jan 20.

Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy.

Alkaptonuria (AKU) is an ultra-rare disease caused by the deficient activity of homogentisate 1,2-dioxygenase enzyme, leading the accumulation of homogentisic acid (HGA) in connective tissues implicating the formation of a black pigmentation called "ochronosis." Although AKU is a multisystemic disease, the most affected tissue is the articular cartilage, which during the pathology appears to be highly damaged. In this study, a model of alkaptonuric chondrocytes and cartilage was realized to investigate the role of HGA in the alteration of the extracellular matrix (ECM). Read More

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Characterizing the alkaptonuria joint and spine phenotype and assessing the effect of homogentisic acid lowering therapy in a large cohort of 87 patients.

J Inherit Metab Dis 2021 May 26;44(3):666-676. Epub 2021 Jan 26.

Department of Musculoskeletal Biology, University of Liverpool, Liverpool, UK.

A large alkaptonuria (AKU) cohort was studied to better characterize the poorly understood spondyloarthropathy of rare disease AKU. Eighty-seven patients attended the National Alkaptonuria Centre (NAC) between 2007 and 2020. Seven only attended once. Read More

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Inflammatory rheumatic diseases in patients with ochronotic arthropathy.

Mod Rheumatol 2021 Feb 2:1-10. Epub 2021 Feb 2.

Faculty of Medicine, Division of Rheumatology, Dokuz Eylul University, Izmir, Turkey.

Background: Ochronotic arthropathy (OcA) refers to excessive homogentisic acid (HGA) deposition in the musculoskeletal system. Our current understanding of OcA is limited, as there are less than a thousand alkaptonuria (AKU) cases reported in the literature. Herein, we investigated the rheumatological manifestations of OcA in a group of adult AKU patients. Read More

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February 2021

A black heart: Aortic valve ochronosis secondary to alkaptonuria causing aortic stenosis.

J Card Surg 2021 Feb 2;36(2):758-760. Epub 2021 Jan 2.

Department of Cardiothoracic Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia.

Alkaptonuria is a rare autosomal recessive genetic disorder where an accumulation of homogentisic acid in the tissues leads to ochronosis-a pathological dark pigmentation. It can affect various tissues and the weight bearing joints of the body, leading to degenerative arthropathy. On the rare occasion, it causes cardiac manifestations. Read More

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February 2021

Exogenous Ochronosis (EO): Skin lightening cream causing rare caviar-like lesion with banana-like pigments; review of literature and histological comparison with endogenous counterpart.

Autops Case Rep 2020 Sep 2;10(4):e2020197. Epub 2020 Sep 2.

University of California, Davis (UC Davis), Department of Pathology and Laboratory Medicine, Sacramento, CA, USA.

Ochronosis is a cutaneous disorder caused by the accumulation of phenols, either endogenously as homogentisic acid in patients with alkaptonuria (autosomal recessive disorder with deficiency of the enzyme homogentisic acid oxidase), or exogenously in patients using phenol products such as topical creams containing hydroquinone or the intramuscular application of antimalarial drugs. Exogenous ochronosis (EO) typically affects the face and was reported in patients with dark skin such as Black South Africans or Hispanics who use skin-lightening products containing hydroquinone for extended periods. Recently more cases have been reported worldwide even in patients with lighter skin tones, to include Eastern Indians, Asians, and Europeans. Read More

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September 2020

Characterising the arthroplasty in spondyloarthropathy in a large cohort of eighty-seven patients with alkaptonuria.

J Inherit Metab Dis 2021 May 20;44(3):656-665. Epub 2020 Dec 20.

Department of Nuclear Medicine, Division of Radiology, Royal Liverpool University Hospital, Liverpool, UK.

Arthroplasty in the spondyloarthropathy (SPOND) of alkaptonuria (AKU) in incompletely characterised. The aim was to improve the understanding of arthroplasty in AKU through a study of patients attending the National Alkaptonuria Centre (NAC). Eighty-seven patients attended the NAC between 2007 and 2020. Read More

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[Ochronosis of the Entire Aortic Root in Alkaptonuria;Report of a Case].

Kyobu Geka 2020 Nov;73(12):1041-1044

Department of Cardiovascular Surgery, Japanese Red Cross Society Himeji Hospital, Himeji, Japan.

Alkaptonuria is a rare hereditary disorder of phenylalanine and tyrosine metabolism, which results in ochronosis of cardiovascular structures including valves, aortic intima, and coronary arteries. Aortic valve disease is the most frequently reported cardiac sequela of alkaptonuria. We report a case of 77-year-old woman with known alkaptonuria who underwent aortic valve replacement for severe aortic stenosis. Read More

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November 2020

Localized argyria with pseudo-ochronosis.

J Cutan Pathol 2020 08;47(8):671-674

Department of Dermatology, The Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.

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Hydroquinone: myths and reality.

Clin Exp Dermatol 2021 Jun 7;46(4):636-640. Epub 2020 Nov 7.

St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, UK.

Hydroquinone has pharmacological uses in disorders of pigmentation because of its ability to competitively inhibit the enzyme tyrosinase. Our contemporary review presents the strongest evidence supporting the use of hydroquinone with the most effective and tolerable formulations combining hydroquinone, retinoid and corticosteroid (modified Kligman formula or 'triple combination cream'). The risk of exogenous ochronosis is low if prescribed concentrations of ≤ 5 for a limited period with regular monitoring. Read More

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Frequency, diagnosis, pathogenesis and management of osteoporosis in alkaptonuria: data analysis from the UK National Alkaptonuria Centre.

Osteoporos Int 2021 May 29;32(5):927-938. Epub 2020 Oct 29.

IACD, University of Liverpool, William Henry Duncan Building, West Derby Street, Liverpool, L7 8TX, UK.

Osteoporosis and fractures are common features of alkaptonuria.

Introduction: A large cohort of alkaptonuria (AKU) patients was studied to better recognise and characterise osteoporosis and fractures in AKU.

Methods: Assessments including questionnaire analysis, DEXA and CT densitometry at the neck of femur (FN), total hip (TH) and lumbar spine (LS) were performed on patients at baseline when 2 mg nitisinone was commenced, and yearly thereafter. Read More

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Anatomical Distribution of Ochronotic Pigment in Alkaptonuric Mice is Associated with Calcified Cartilage Chondrocytes at Osteochondral Interfaces.

Calcif Tissue Int 2021 02 14;108(2):207-218. Epub 2020 Oct 14.

Department of Musculoskeletal & Ageing Science, Institute of Life Course and Medical Science, University of Liverpool, William Henry Duncan Building, 6 West Derby Street, Liverpool, L7 8TX, UK.

Alkaptonuria (AKU) is characterised by increased circulating homogentisic acid and deposition of ochronotic pigment in collagen-rich connective tissues (ochronosis), stiffening the tissue. This process over many years leads to a painful and severe osteoarthropathy, particularly affecting the cartilage of the spine and large weight bearing joints. Evidence in human AKU tissue suggests that pigment binds to collagen. Read More

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February 2021

Minimally invasive endoscopic aortic valve replacement for alkaptonuria-associated severe aortic stenosis: a case report and literature review.

Gen Thorac Cardiovasc Surg 2021 Mar 24;69(3):605-609. Epub 2020 Sep 24.

Department of Cardiovascular Surgery, Sasebo Central Hospital, 15 Yamato-cho, Sasebo, Nagasaki, 857-1195, Japan.

Alkaptonuria is an inherited metabolic disease caused by a genetic deficiency of homogentisate 1,2-dioxygenase and characterized by dark-brown connective tissue related to the deposition of oxidized homogentisic acid. Pigment deposition is also observed in the cardiovascular system, such as in the coronary arteries, cardiac valves, and aorta. Because aortic stenosis may develop secondary to pigment deposition-related calcification at the aortic valve, aortic valve replacement may be necessary for severe aortic valve disease. Read More

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Hip and knee replacement in patients with ochronosis: Clinical experience and literature review.

Orthop Rev (Pavia) 2020 Jun 26;12(Suppl 1):8687. Epub 2020 Jun 26.

Department of Orthopedics, Fondazione Policlinico Universitario Agostino Gemelli IRCCS; Università Cattolica del Sacro Cuore, Rome.

Patients with alkaptonuria can present ochronotic degenerative arthropathy due to the accumulation of pigments in the cartilages. Ochronotic arthropathy initially affects the spine, then there is the involvement of the other large joints, with greater frequency of the knees. In this article we will present two patients with alkaptonuria who have been effectively treated with knee and hip replacement, comparing our experience with what is available in the literature. Read More

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Cervical Myelopathy Due to Ochronosis: An Intraoperative Suspicion.

Am J Case Rep 2020 Sep 10;21:e924575. Epub 2020 Sep 10.

Department of Special Surgery, Division of Orthopaedics, School of Medicine, The University of Jordan, Amman, Jordan.

BACKGROUND Alkaptonuria (AKU) is a rare metabolic disease caused by a deficiency in homogentisic acid oxidase, which leads to the accumulation of homogentisic acid dark pigments in tissues such as bones, ligaments, and tendons. Long-term duration of this condition, termed ochronosis, can result in degenerative arthropathy involving the spine and large joints. CASE REPORT This report describes a 55-year-old Jordanian woman presenting with chronic neck and lower back pain. Read More

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September 2020

Reversal of ochronotic pigmentation in alkaptonuria following nitisinone therapy: Analysis of data from the United Kingdom National Alkaptonuria Centre.

JIMD Rep 2020 Sep 22;55(1):75-87. Epub 2020 Jun 22.

Institute of Ageing and Chronic Disease, Musculoskeletal Biology I, William Henry Duncan Building Liverpool UK.

Background: Increased homogentisic acid (HGA) causes ochronosis. Nitisinone decreases HGA. The aim was to study the effect of nitisinone on the ochronosis progression. Read More

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September 2020

Long-Term Outcomes of the Knee and Hip Arthroplasties in Patients with Alkaptonuria.

Arthroplast Today 2020 Dec 23;6(4):689-693. Epub 2020 Aug 23.

Department of Pharmacology, Faculty of Medicine, Mu'tah University, Karak, Jordan.

Alkaptonuria is a rare autosomal recessive metabolic disorder. It is characterized by the accumulation of homogentisic acid in the body due to a lack of enzymes that degrade it. Over time, it results in joint degeneration and eventually leads to ochronosis. Read More

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December 2020

Transient pockets as mediators of gas molecules routes inside proteins: The case study of dioxygen pathway in homogentisate 1,2-dioxygenase and its implication in Alkaptonuria development.

Comput Biol Chem 2020 Oct 6;88:107356. Epub 2020 Aug 6.

Department of Biotechnology, Chemistry and Pharmacy, University of Siena, via Aldo Moro 2, 53100, Siena, Italy.

Alkaptonuria (AKU) is an ultra-rare disease caused by mutations in homogentisate 1,2-dioxygenase (HGD) enzyme, characterized by the loss of enzymatic activity and the accumulation of its substrate, homogentisic acid (HGA) in different tissues, leading to ochronosis and organ degeneration. Although the pathological effects of HGD mutations are largely studied, less is known about the structure of the enzyme, in particular the pathways for dioxygen diffusion to the active site, required for the enzymatic reaction, are still uninvestigated. In the present project, the combination of two in silico techniques, Molecular Dynamics (MD) simulation and Implicit Ligand Sampling (ILS), was used to delineate gas diffusion routes in HGD enzyme. Read More

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October 2020

Efficacy and safety of once-daily nitisinone for patients with alkaptonuria (SONIA 2): an international, multicentre, open-label, randomised controlled trial.

Lancet Diabetes Endocrinol 2020 09 18;8(9):762-772. Epub 2020 Aug 18.

Swedish Orphan Biovitrum, Stockholm, Sweden.

Background: Alkaptonuria is a rare, genetic, multisystem disease characterised by the accumulation of homogentisic acid (HGA). No HGA-lowering therapy has been approved to date. The aim of SONIA 2 was to investigate the efficacy and safety of once-daily nitisinone for reducing HGA excretion in patients with alkaptonuria and to evaluate whether nitisinone has a clinical benefit. Read More

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September 2020