Alkaptonuria

An inborn error of amino acid metabolism resulting from a defect in the enzyme HOMOGENTISATE 1,2-DIOXYGENASE, an enzyme involved in the breakdown of PHENYLALANINE and TYROSINE. It is characterized by accumulation of HOMOGENTISIC ACID in the urine, OCHRONOSIS in various tissues, and ARTHRITIS.

Also Known As:

Networked: 496 relevant articles (8 outcomes, 34 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Tyrosinemias (Tyrosinemia)
2.	Pain (Aches)
3.	Low Back Pain (Lumbago)
4.	Radiculopathy (Radiculopathy, Cervical)
5.	Rheumatic Diseases (Rheumatism)

Experts

1.	Santucci, Annalisa: 42 articles (01/2022 - 10/2010)
2.	Ranganath, Lakshminarayan R: 33 articles (07/2022 - 02/2011)
3.	Gallagher, James A: 30 articles (07/2022 - 10/2010)
4.	Braconi, Daniela: 29 articles (01/2022 - 10/2010)
5.	Bernardini, Giulia: 28 articles (01/2022 - 10/2010)
6.	Millucci, Lia: 27 articles (01/2022 - 10/2010)
7.	Ranganath, L R: 25 articles (06/2022 - 02/2010)
8.	Gallagher, J A: 23 articles (06/2022 - 11/2008)
9.	Milan, Anna M: 18 articles (07/2022 - 01/2015)
10.	Hughes, Andrew T: 17 articles (07/2022 - 01/2015)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Alkaptonuria:

1.	nitisinone (Orfadin)FDA Link 01/01/2019 - "To study the efficacy of low dosage of nitisinone in alkaptonuria. " 06/01/2005 - "We investigated the safety and the HGA-depleting efficacy of nitisinone in an open-label, single-center study of 9 alkaptonuria patients (5 women, 4 men; 35-69 years of age) over the course of 3 to 4 months. " 01/01/2019 - "Efficacy of low dose nitisinone in the management of alkaptonuria." 11/18/2022 - "Effects of Nitisinone on Oxidative and Inflammatory Markers in Alkaptonuria: Results from SONIA1 and SONIA2 Studies." 10/19/2022 - "The present study is the first ever to systematically analyze the baseline clinical data of 24 AKU sibling pairs/groups collected in the SONIA 2 (Suitability Of Nitisinone In Alkaptonuria 2) study to evaluate phenotypical differences between patients carrying the same HGD genetic variants. "
2.	Homogentisic AcidIBA 01/01/2020 - "Homogentisic acid is not only eliminated by glomerular filtration and tubular secretion but also produced in the kidney in alkaptonuria." 10/01/1965 - "Studies of alcaptonuria: infra-red spectra of deuterated homogentisic acid solutions." 07/01/1960 - "Studies of alcaptonuria: kinetics of homogentisic acid autoxidation." 01/01/1947 - "Studies on alcaptonuria; the estimation of homogentisic acid." 01/01/1947 - "Studies on alcaptonuria: 1. The estimation of homogentisic acid."
3.	Tyrosine (L-Tyrosine)FDA Link 07/01/2022 - "Metabolomic studies in the inborn error of metabolism alkaptonuria reveal new biotransformations in tyrosine metabolism." 11/01/2023 - "Alkaptonuria (AKU) was used as a tyrosine-inherited metabolic disorder reference disease with non-hepatic manifestations. " 05/01/2023 - "Alkaptonuria (AKU) is a rare hereditary disorder of tyrosine degradation. " 09/25/2022 - "Articles in this issue discuss metabolites of tyrosine catabolism in healthy patients and those with alkaptonuria." 01/01/2022 - "Alkaptonuria (AKU) is a rare autosomal recessive disorder in which tyrosine metabolism is altered. "
4.	Phenylalanine (L-Phenylalanine)FDA Link 01/01/2003 - "Alkaptonuria (AKU) is a rare metabolic disorder of phenylalanine catabolism that is inherited as an autosomal recessive trait. " 07/15/1997 - "Alkaptonuria (AKU; McKusick No. 203500), a rare hereditary disorder of the phenylalanine catabolism, was the first disease to be interpreted as an inborn error of metabolism (A. " 01/01/2018 - "Alkaptonuria is a hereditary disorder of phenylalanine and tyrosine, with an incidence of approximately 1/200,000 to 1/1,000,000. " 12/01/2013 - "Alkaptonuria (AKU) is an ultra-rare metabolic disorder of the catabolic pathway of tyrosine and phenylalanine that has been poorly characterized at molecular level. " 04/01/1998 - "Alkaptonuria (AKU), a rare hereditary disorder of phenylalanine and tyrosine catabolism, was the first disease to be interpreted as an inborn error of metabolism. "
5.	DioxygenasesIBA 01/01/2013 - "Alkaptonuria is an autosomal recessive disorder caused by the deficiency of homogentisate 1.2 dioxygenase activity. " 06/30/1998 - "Alkaptonuria (AKU) is caused by lack of homogentisate 1, 2 dioxygenase (HGO) activity. " 10/25/2023 - "Alkaptonuria is a very rare disorder in which homogentisic acid accumulates due to a deficiency in the activity of homogentisic acid 1,2 dioxygenase. " 04/15/2019 - "Endogenous ochronosis (EO) or alkaptonuria is an inherited autosomal recessive disease caused by the insufficiency of the enzyme homogentisic acid dioxygenase. " 01/01/1999 - "In the present study, 2(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), a potent inhibitor of p-hydroxyphenylpyruvate dioxygenase (which catalyzes the formation of homogentisic acid from p-hydroxyphenylpyruvic acid) was adopted as a possible therapeutic agent for alkaptonuria. "
6.	HerbicidesIBA 12/09/2005 - "While several di- and tri-ketone alkaloids are known as inhibitors of HPPD and used commercially as herbicides, one such inhibitor, [2-nitro-4-(trifluoromethyl)benzoyl]-1,3-cyclohexanedione (NTBC), has also been used therapeutically to treat type I tyrosinemia and alkaptonuria in humans. " 04/05/2016 - "Inhibition of para-Hydroxyphenylpyruvate Dioxygenase by Analogues of the Herbicide Nitisinone As a Strategy to Decrease Homogentisic Acid Levels, the Causative Agent of Alkaptonuria." 08/15/2005 - "In this bacterium, deletion of the homogentisate gene cluster (hmgRABC) confers upon this mutant huge biotechnological possibilities since it can be used: (i) as a target for testing new specific herbicides (p-hydroxy-phenylpyruvate dioxygenase inhibitors); (ii) to identify new therapeutic drugs-effective in the treatment of alkaptonuria and other related tyrosinemia - and (iii) as a source of homogentisic acid in a plant-bacterium association."
7.	Therapeutic UsesIBA 01/01/2012 - ", there is no proven treatment for alkaptonuria but emergence of orphan drug legislation internationally has promoted the licensing of nitisinone (Orfadin™) for an equally rare disorder of tyrosine metabolism - hereditary tyrosinaemia type 1. Nitisinone, a triketone competitive inhibitor of a proximal step leading to the formation of homogentisic acid, has potent therapeutic effects in hereditary tyrosinemia and rapidly ameliorates the primary biochemical abnormality in patients with alkaptonuria.Here"
8.	phenylpyruvic acidIBA 08/15/2005 - "In this bacterium, deletion of the homogentisate gene cluster (hmgRABC) confers upon this mutant huge biotechnological possibilities since it can be used: (i) as a target for testing new specific herbicides (p-hydroxy-phenylpyruvate dioxygenase inhibitors); (ii) to identify new therapeutic drugs-effective in the treatment of alkaptonuria and other related tyrosinemia - and (iii) as a source of homogentisic acid in a plant-bacterium association."
9.	CollagenIBA 01/01/1962 - "Biochemical studies on the pathogenesis of collagen tissue changes in alcaptonuria." 01/01/1960 - "Studies on the pathogenesis of collagen tissue changes in alcaptonuria." 01/01/2020 - "Pigmentation Chemistry and Radical-Based Collagen Degradation in Alkaptonuria and Osteoarthritic Cartilage." 12/01/2011 - "Collagen atomic scale molecular disorder in ochronotic cartilage from an alkaptonuria patient, observed by solid state NMR." 11/01/1987 - "A feature of alkaptonuria previously unreported in the English-language literature was the presence of phagocytosis of large collagen fibrils by synovial macrophages in both cases. "
10.	Homogentisate 1,2-Dioxygenase (Homogentisate 1,2 Dioxygenase)IBA 06/01/2012 - "This study was conducted to identify mutations in the homogentisate 1,2 dioxygenase gene (HGD) in alkaptonuria patients among Jordanian population. " 01/01/2023 - "Alkaptonuria (AKU) is a rare autosomal recessive metabolic disorder caused by pathogenic variants in the homogentisate 1,2-dioxygenase (HGD) gene. " 01/01/2023 - "Homogentisate 1,2-dioxygenase (HGD) gene variants in young Egyptian patients with alkaptonuria." 11/14/2022 - "A robust bacterial high-throughput screening system to evaluate single nucleotide polymorphisms of human homogentisate 1,2-dioxygenase in the context of alkaptonuria." 10/19/2022 - "Alkaptonuria (AKU) is a rare autosomal recessive disorder caused by mutations within a gene coding for homogentisate 1,2-dioxygenase (HGD). "

Therapies and Procedures

1.	Therapeutics 11/19/2021 - "Such evidence opens the way for molecular investigation of HGA fate in cells and tissue aiming to find new targets for Alkaptonuria therapy." 09/01/2015 - "Progress in Alkaptonuria--are we near to an effective therapy?" 09/01/2013 - "Alkaptonuria (AKU) is an ultra-rare autosomal recessive disease that currently lacks an appropriate therapy. " 12/26/2002 - "The reported data on the natural history of alkaptonuria provide a basis for the evaluation of long-term therapies. " 06/01/2021 - "Development of an Effective Therapy for Alkaptonuria - Lessons for Osteoarthritis."
2.	Diet Therapy (Therapy, Diet) 10/01/2023 - "Alkaptonuria is typically managed supportively with pain medication, dietary modifications, and surgical interventions, which are considered to be the gold standard of therapy. " 09/01/2007 - "Alkaptonuria is treated symptomatically, surgical intervention necessitates in advanced stages, treatment with ascorbic acid (Vitamin C) and dietary restrictions of food containing phenylalanine and tyrosine have proved to be successful in alleviating the symptoms." 01/01/2020 - "Dietary restriction of tyrosine and phenylalanine lowers tyrosinemia associated with nitisinone therapy of alkaptonuria."
3.	Conservative Treatment 08/01/2023 - "We present one such rare case of alkaptonuria in a 31-year-old female presenting with low back pain and left leg radiculopathy not relieved with conservative management. "
4.	Arthroplasty 01/01/2021 - "The aim was to improve the understanding of arthroplasty in AKU through a study of patients attending the National Alkaptonuria Centre (NAC). " 12/01/2020 - "Long-Term Outcomes of the Knee and Hip Arthroplasties in Patients with Alkaptonuria." 04/01/1990 - "Bilateral hip arthroplasty in alkaptonuria." 01/01/2022 - "Total Shoulder Reverse Arthroplasty in Alkaptonuria: An Effective Option to Treat a Complication of a Rare Disease." 01/01/2021 - "Arthroplasty in the spondyloarthropathy (SPOND) of alkaptonuria (AKU) in incompletely characterised. "
5.	Transcatheter Aortic Valve Replacement 01/04/2022 - "We present a case of near infrared spectroscopy failing to accurately monitor cerebral oximetry in a woman, with alkaptonuria, undergoing a transcatheter aortic valve implantation." 01/01/2023 - "Alkaptonuria: A rare cause of severe aortic stenosis treated by transcatheter aortic valve replacement." 12/01/2019 - "This report of transcatheter aortic valve replacement for treating alkaptonuria-associated aortic stenosis expands the potential treatment options for these patients." 12/01/2019 - "Transcatheter Aortic Valve Replacement for Alkaptonuria-Associated Aortic Stenosis."