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alkaptonuria

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https://www.readbyqxmd.com/read/29147990/assessment-of-the-effect-of-once-daily-nitisinone-therapy-on-24-h-urinary-metadrenalines-and-5-hydroxyindole-acetic-acid-excretion-in-patients-with-alkaptonuria-after-4-weeks-of-treatment
#1
A S Davison, B Norman, A M Milan, A T Hughes, M Khedr, J Rovensky, J A Gallagher, L R Ranganath
BACKGROUND: One of the major metabolic consequences of using nitisinone to treat patients with alkaptonuria is that circulating tyrosine concentrations increase. As tyrosine is required for the biosynthesis of catecholamine neurotransmitters, it is possible that their metabolism is altered as a consequence. Herein we report the 24-h urinary excretion of normetadrenaline (NMA), metadrenaline (MA), 3-methoxytyramine (3-MT) (catecholamine metabolites) and 5-hydroxyindole acetic acid (5-HIAA, metabolite of serotonin) in a cohort of AKU patients before and after a 4-week treatment trial with nitisinone...
November 17, 2017: JIMD Reports
https://www.readbyqxmd.com/read/29113706/calcaneal-avulsion-of-an-ochronotic-achilles-tendon-a-case-report
#2
Oğuzhan Tanoğlu, Gökhun Arıcan, Ahmet Özmeriç, Kadir Bahadır Alemdaroğlu, Muzaffer Çaydere
Alkaptonuria is a hereditary disorder of phenylalanine and tyrosine, with an incidence of approximately 1/200,000 to 1/1,000,000. Ochronosis is the accumulation of homogentisic acid and its metabolites in connective tissues such as the tendons, cartilage, and skin. In the present case study, a 50-year-old male presented with a nontraumatic calcaneal avulsion without a previous diagnosis of ochronosis. To the best of our knowledge, little information has been reported of this pathology in the Achilles tendon and the surgical management...
November 4, 2017: Journal of Foot and Ankle Surgery: Official Publication of the American College of Foot and Ankle Surgeons
https://www.readbyqxmd.com/read/28942493/asymptomatic-corneal-keratopathy-secondary-to%C3%A2-hypertyrosinaemia-following-low-dose-nitisinone-and%C3%A2-a%C3%A2-literature-review-of-tyrosine-keratopathy-in%C3%A2-alkaptonuria
#3
M Khedr, S Judd, M C Briggs, A T Hughes, A M Milan, R M K Stewart, E A Lock, J A Gallagher, L R Ranganath
Nitisinone, although unapproved for use in alkaptonuria (AKU), is currently the only homogentisic acid lowering therapy with a potential to modify disease progression in AKU. Therefore, safe use of nitisinone off-label requires identifying and managing tyrosine keratopathy. A 22-year-old male with AKU commenced 2 mg daily nitisinone after full assessment. He was issued an alert card explaining potential ocular symptoms such as red eye, tearing, ocular pain and visual impairment and how to manage them. On his first and second annual follow-up visits to the National Alkaptonuria Centre (NAC), there was no corneal keratopathy on slit lamp examination...
September 24, 2017: JIMD Reports
https://www.readbyqxmd.com/read/28879639/nitisinone-induced-keratopathy-in-alkaptonuria-a-challenging-diagnosis-despite-clinical-suspicion
#4
Andrew White, Michel C Tchan
Alkaptonuria is a rare disorder of amino acid metabolism that causes premature large joint and spine arthropathy and cardiac valvular disease. It is characterised by elevated levels of homogentisic acid. Nitisinone (NTBC) is a benzoylcyclohexane-1,3-dione that reversibly inhibits the activity of the enzymatic step immediately prior to homogentisate dioxygenase, hence reducing the production of homogentisic acid. Thus it is thought that nitisinone might be a treatment for alkaptonuria. A side effect of NTBC therapy is elevation of plasma tyrosine levels in a manner analogous to tyrosinemia type 2, another related condition which causes a painful palmoplantar hyperkeratosis and eye pathology described as conjunctivitis and herpetic-like corneal ulceration...
September 7, 2017: JIMD Reports
https://www.readbyqxmd.com/read/28878548/arthroscopic-diagnosis-and-treatment-of-shoulder-ochronotic-arthropathy-a-case-report
#5
Prateek Kumar Gupta, Ashis Acharya, Dhananjay Sabat, Amit Mourya
Alkaptonuria is a rare inherited metabolic disorder, caused by the deficiency of homogentisate 1,2 dioxygenase enzyme. The three major features of alkaptonuria are the presence of homogentisic acid in urine, ochronosis (bluish-black pigmentation in connective tissue) and arthritis of the spine and large joints. We present a 48 years old female presented with pain, restriction of movements of right shoulder. Arthroscopy was suggestive of ochronotic arthropathy. The definitive diagnosis of ochronosis was subsequently confirmed by laboratory and pathologic evaluation...
August 2017: Journal of Clinical Orthopaedics and Trauma
https://www.readbyqxmd.com/read/28869836/toward-a-generalized-computational-workflow-for-exploiting-transient-pockets-as-new-targets-for-small-molecule-stabilizers-application-to-the-homogentisate-1-2-dioxygenase-mutants-at-the-base-of-rare-disease-alkaptonuria
#6
Andrea Bernini, Silvia Galderisi, Ottavia Spiga, Giulia Bernardini, Neri Niccolai, Fabrizio Manetti, Annalisa Santucci
Alkaptonuria (AKU) is an inborn error of metabolism where mutation of homogentisate 1,2-dioxygenase (HGD) gene leads to a deleterious or misfolded product with subsequent loss of enzymatic degradation of homogentisic acid (HGA) whose accumulation in tissues causes ochronosis and degeneration. There is no licensed therapy for AKU. Many missense mutations have been individuated as responsible for quaternary structure disruption of the native hexameric HGD. A new approach to the treatment of AKU is here proposed aiming to totally or partially rescue enzyme activity by targeting of HGD with pharmacological chaperones, i...
August 25, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28813744/alkaptonuria-a-case-report-with-diagnostic-challenge
#7
Vasantha L Gali, Amy M Kerkvliet, Jacob M Kusmak, Jana K Elwood
Alkaptonuria is a rare autosomal recessive metabolic disorder caused by deficiency of homogentisic acid (HGA) oxidase, the only enzyme capable of catabolizing HGA. Deficiency of this enzyme leads to excess HGA which deposits in the connective tissue. We present a case of a 64-year-old woman who was referred to the dermatology clinic for a full body mole check and skin cancer screening. Clinically she had blue/gray pigmentation of the external ear and sclera. Also she had a domed papule on the left cheek with punctate gray pigmentation which was biopsied...
August 2017: South Dakota Medicine: the Journal of the South Dakota State Medical Association
https://www.readbyqxmd.com/read/28709382/severe-aortic-valve-stenosis-due-to-alkaptonuric-ochronosis
#8
Magdy M El-Sayed Ahmed, Omar Hussain, David A Ott, Muhammad Aftab
Alkaptonuric ochronosis is a rare cause of aortic valve stenosis. We report the case of a 61-year-old female patient with alkaptonuria who presented to our institute with the clinical picture of severe aortic valve stenosis, which was confirmed by transthoracic echocardiography. On aortotomy, she was noted to have an impressive black discoloration of ascending aorta and the aortic root complex involving the aortic valve leaflets. She underwent an uneventful aortic valve replacement. She was discharged home 10 days postoperatively...
July 1, 2017: Seminars in Cardiothoracic and Vascular Anesthesia
https://www.readbyqxmd.com/read/28690378/molecular-docking-analysis-of-nitisinone-with-homogentisate-1-2-dioxygenase
#9
Narges Zolfaghari
Alkaptonuria is an inherited disease that is caused by homogenticate accumulation. Deficiency or mutation in Homogentisate 1,2 dioxygenase gene (chromosome 3q21-q23) leads to production of incorrectly folded or truncated enzyme. Several studies indicated that competitive inhibitors of Homogentisate 1,2 dioxygenase like Nitisinone could be used for Alkaptonuria treatment. Therefore, it is of interest to design better inhibitors of the enzyme. We used subset 3_p.0.5 from Zinc database as the virtual screening library by PyRx software relaying on Lamarckian genetics algorithm...
2017: Bioinformation
https://www.readbyqxmd.com/read/28643719/alkaptonuria-a-case-report
#10
Nirupama Damarla, Prathima Linga, Mallika Goyal, Sanjay Reddy Tadisina, G Satyanarayana Reddy, Hymavathi Bommisetti
Alkaptonuria is a rare inborn error of metabolism with autosomal recessive inheritance with a mutation in homogentisate 1,2-dioxygenase. It results in accumulation of homogentisic acid in connective tissues (ochronosis). Most common ocular manifestations are bluish-black discoloration of the conjunctiva, cornea, and sclera. In this case report, a 39-year-old Indian male patient with additional ocular features in the retina is described.
June 2017: Indian Journal of Ophthalmology
https://www.readbyqxmd.com/read/28535941/-anesthetic-management-of-two-patients-with-alkaptonuric-ochronosis-for-total-knee-arthroplasty
#11
Betul Kozanhan
The current case report describes two cases of alkaptonuric ochronosis for anesthetic management. Alkaptonuria is a rare genetic orphan disease of tyrosine metabolism characterized by an accumulation of homogentisic acid in cartilage and connective tissues. Patients present most commonly for orthopedic joint surgery due to progressive arthropathy that can be misdiagnosed many a times. However respiratory, airway, cardiovascular and genitourinary systems complications can occur with age progressing. Restricted range of motion of cervical spine may lead to difficulty with airway management...
May 20, 2017: Revista Brasileira de Anestesiologia
https://www.readbyqxmd.com/read/28528068/aortic-valve-stenosis-in-alkaptonuria
#12
Christos Tourmousoglou, Nikolaos Nikoloudakis, Antonis Pitsis
No abstract text is available yet for this article.
June 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28492150/selective-screening-for-organic-acidurias-and-amino-acidopathies-in-pakistani-children
#13
Noreen Abbas Sherazi, Aysha Habib Khan, Lena Jafri, Azeema Jamil, Nasir Ali Khan, Bushra Afroze
OBJECTIVE: To determine the frequency of organic acidurais (OA) and amino acidopathies (AA) in selected high-risk patients screened in two years. STUDY DESIGN: Retrospective Observational study. PLACE AND DURATION OF STUDY: The Aga Khan University Hospital (AKUH), Karachi, from January 2013 to December 2014. METHODOLOGY: Patients with OA and AA were included in the study and patients with IMDs other than OA and AA were excluded...
April 2017: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://www.readbyqxmd.com/read/28410607/aprecisekure-an-approach-of-precision-medicine-in-a-rare-disease
#14
Ottavia Spiga, Vittoria Cicaloni, Andrea Bernini, Andrea Zatkova, Annalisa Santucci
BACKGROUND: Alkaptonuria (AKU; OMIM:203500) is a classic Mendelian genetic disorder described by Garrod already in 1902. It causes urine to turn black upon exposure to air and also leads to ochronosis as well as early osteoarthritis. Our objective is the implementation of a Precision Medicine (PM) approach to AKU. We present here a novel ApreciseKUre database facilitating the collection, integration and analysis of patient data in order to create an AKU-dedicated "PM Ecosystem" in which genetic, biochemical and clinical resources can be shared among registered researchers...
April 14, 2017: BMC Medical Informatics and Decision Making
https://www.readbyqxmd.com/read/28271171/histological-and-ultrastructural-characterization-of-alkaptonuric-tissues
#15
Lia Millucci, Giulia Bernardini, Adriano Spreafico, Maurizio Orlandini, Daniela Braconi, Marcella Laschi, Michela Geminiani, Pietro Lupetti, Giovanna Giorgetti, Cecilia Viti, Bruno Frediani, Barbara Marzocchi, Annalisa Santucci
Alkaptonuria (AKU) is a hereditary disorder that results from altered structure and function of homogentisate 1,2 dioxygenase (HGD). This enzyme, predominantly produced by liver and kidney, is responsible for the breakdown of homogentisic acid (HGA), an intermediate in the tyrosine degradation pathway. A deficient HGD activity causes HGA levels to rise systemically. The disease is clinically characterized by homogentisic aciduria, bluish-black discoloration of connective tissues (ochronosis) and joint arthropathy...
March 7, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/28240677/an-unusual-cause-of-myelopathy-ochronotic-spondyloarthropathy-with-positive-hla-b27
#16
Sinem Bozkurt, Lale Aktekin, Fatma Gülçin Uğurlu, Serdar Balci, Nebahat Sezer, Selami Akkus
Ochronosis is a late developing complication of alkaptonuria, a black brownish pigment in the fibrous and cartilaginous tissues. Although most previous studies reported alkaptonuria and back pain due to ochronosis, thoracic myelopathy is an extremely rare complication. In this report, a paraparetic patient who has ochronotic spondiloarthropathy with the presence of HLA B27 antigen is described. He had low back and leg pain and morning stiffness for 5 yrs. Last year, these were followed by tingling, numbness, and weakness the in lower extremities and he was operated on with preliminary diagnosis of prolapsed disc herniation and cord compression...
November 2017: American Journal of Physical Medicine & Rehabilitation
https://www.readbyqxmd.com/read/28217270/neurological-assessment-and-nerve-conduction-study-findings-in-22-patients-with-alkaptonuria-from-jordan
#17
Omar Alrawashdeh, Mohammad Alsbou, Hamed Alzoubi, Hani Al-Shagahin
Alkaptonuria is a rare metabolic disease characterised by accumulative deposition of homogentisic acid in the connective tissue of the body. This results in early degeneration of tendons, cartilages, heart valves, and other tissues. The main objective of the study is to examine the possibility of the nervous system involvement in patients with alkaptonuria The sample consists of two groups; 22 patients with AKU and 20 controls. A neurological assessment has been carried out including detailed medical history, neurological examination, and a nerve conduction study of the nerves of the dominant hand...
November 2, 2016: Neurology International
https://www.readbyqxmd.com/read/28192171/a-new-light-on-alkaptonuria-a-fourier-transform-infrared-microscopy-ftirm-and-low-energy-x-ray-fluorescence-lexrf-microscopy-correlative-study-on-a-rare-disease
#18
Elisa Mitri, Lia Millucci, Lucia Merolle, Giulia Bernardini, Lisa Vaccari, Alessandra Gianoncelli, Annalisa Santucci
BACKGROUND: Alkaptonuria (AKU) is an ultra-rare disease associated to the lack of an enzyme involved in tyrosine catabolism. This deficiency results in the accumulation of homogentisic acid (HGA) in the form of ochronotic pigment in joint cartilage, leading to a severe arthropathy. Secondary amyloidosis has been also unequivocally assessed as a comorbidity of AKU arthropathy. Composition of ochronotic pigment and how it is structurally related to amyloid is still unknown. METHODS: We exploited Synchrotron Radiation Infrared and X-Ray Fluorescence microscopies in combination with conventional bio-assays and analytical tools to characterize chemical composition and morphology of AKU cartilage...
May 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28158906/reduced-primary-cilia-length-and-altered-arl13b-expression-are-associated-with-deregulated-chondrocyte-hedgehog-signaling-in-alkaptonuria
#19
Stephen D Thorpe, Silvia Gambassi, Clare L Thompson, Charmilie Chandrakumar, Annalisa Santucci, Martin M Knight
Alkaptonuria (AKU) is a rare inherited disease resulting from a deficiency of the enzyme homogentisate 1,2-dioxygenase which leads to the accumulation of homogentisic acid (HGA). AKU is characterized by severe cartilage degeneration, similar to that observed in osteoarthritis. Previous studies suggest that AKU is associated with alterations in cytoskeletal organization which could modulate primary cilia structure/function. This study investigated whether AKU is associated with changes in chondrocyte primary cilia and associated Hedgehog signaling which mediates cartilage degradation in osteoarthritis...
September 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28128559/4-hydroxyphenylpyruvate-dioxygenase-and-its-inhibition-in-plants-and-animals-small-molecules-as-herbicides-and-agents-for-the-treatment-of-human-inherited-diseases
#20
REVIEW
Annalisa Santucci, Giulia Bernardini, Daniela Braconi, Elena Petricci, Fabrizio Manetti
This review mainly focuses on the physiological function of 4-hydroxyphenylpyruvate dioxygenase (HPPD), as well as on the development and application of HPPD inhibitors of several structural classes. Among them, one illustrative example is represented by compounds belonging to the class of triketone compounds. They were discovered by serendipitous observations on weed growth and were developed as bleaching herbicides. Informed reasoning on nitisinone (NTBC, 14), a triketone that failed to reach the final steps of the herbicidal design and development process, allowed it to become a curative agent for type I tyrosinemia (T1T) and to enter clinical trials for alkaptonuria...
May 25, 2017: Journal of Medicinal Chemistry
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