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Indian Journal of Ophthalmology Jun 2017Alkaptonuria is a rare inborn error of metabolism with autosomal recessive inheritance with a mutation in homogentisate 1,2-dioxygenase. It results in accumulation of...
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.
Topics: Adult; Alkaptonuria; Conjunctiva; Cornea; Diagnosis, Differential; Eye Diseases; Humans; Male; Ochronosis; Retina; Sclera; Tomography, Optical Coherence
PubMed: 28643719
DOI: 10.4103/ijo.IJO_337_16 -
Nuclear Medicine Communications Oct 2011Alkaptonuria is a rare autosomal recessive disorder due to a lack of the enzyme homogentisate dioxygenase, leading to ochronosis, a process of accumulation of a... (Review)
Review
Alkaptonuria is a rare autosomal recessive disorder due to a lack of the enzyme homogentisate dioxygenase, leading to ochronosis, a process of accumulation of a melanin-like polymer of homogentisic acid in cartilage and other collagenous structures. Patients develop severe osteoarthropathy that resembles osteoarthritis. Although the diagnosis of alkaptonuria is not particularly challenging in view of the blue-black discolouration of visible connective tissue and the presence of homogentisic acid in urine, the natural history of alkaptonuria remains poorly understood. Patients would benefit immensely from an objective assessment of their disease status and from a clearer understanding of the pathophysiology and associated physical changes. Isotope bone scans, which are commonly used to identify the extent of involvement of bones in cancerous processes, have also been increasingly used for characterizing the extent of arthropathy in conditions such as osteoarthritis and rheumatoid arthritis. Semiquantitative scores based on the extent of involvement of joints have been used to describe the involvement of large joints in the context of symptomatic treatment for osteoarthritis. A similar semiquantitative isotope bone scan score depending on the involvement of the number of large joints in patients with alkaptonuria can be formulated and validated in a suitable cohort of patients. Bone densitometry measurement using dual-energy X-ray absorptiometry scanning is an internationally accepted tool to assess the risk and extent of osteoporosis, and is increasingly used to assess the additional fracture risk in patients with arthropathy. We believe that, currently, nuclear medicine techniques can provide useful information, which can be incorporated into disease severity scores for alkaptonuria. Once the biological basis for alkaptonuria is better understood, it is feasible that nuclear medicine techniques of even greater sensitivity and specificity can be developed, thereby taking advantage of the vast advances in the fields of radiochemistry, radiopharmacy, positron emission tomography-computed tomography and positron emission tomography-magnetic resonance imaging scanning.
Topics: Alkaptonuria; Diagnostic Imaging; Humans; Joint Diseases; Nuclear Medicine
PubMed: 21876398
DOI: 10.1097/MNM.0b013e32834955df -
BMJ (Clinical Research Ed.) Sep 2011
Topics: Alkaptonuria; History, 20th Century; History, 21st Century; Humans; Male; Pain; United Kingdom
PubMed: 21964346
DOI: 10.1136/bmj.d5155 -
Eklem Hastaliklari Ve Cerrahisi = Joint... Dec 2019Alkaptonuria is an autosomal recessive disease caused by the accumulation of homogentisic acid (HGA) products in the ligament, cartilage, skin and various organs due to...
Alkaptonuria is an autosomal recessive disease caused by the accumulation of homogentisic acid (HGA) products in the ligament, cartilage, skin and various organs due to the lack of HGA oxidase enzyme. In this article, we present a 61-year-old male patient operated on due to a diagnosis of spontaneous Achilles tendon rupture and diagnosed as alkaptonuria due to the intraoperative color of the tissues and the subsequent examinations. We also reviewed alkaptonuria and its accompanying pathologies in light of the literature.
Topics: Accidental Falls; Achilles Tendon; Alkaptonuria; Diagnosis, Differential; Humans; Male; Middle Aged; Ochronosis; Rupture, Spontaneous
PubMed: 31650933
DOI: 10.5606/ehc.2019.66155 -
Journal of Inherited Metabolic Disease Sep 2019Ochronosis is the process in alkaptonuria (AKU) that causes all the debilitating morbidity. The process involves selective deposition of homogentisic acid (HGA)-derived... (Review)
Review
Ochronosis is the process in alkaptonuria (AKU) that causes all the debilitating morbidity. The process involves selective deposition of homogentisic acid (HGA)-derived pigment in tissues altering the properties of these tissues, leading to their failure. Some tissues like cartilage are more easily affected by ochronosis while others such as the liver and brain are unaffected for reasons that are still not understood. In vitro and mouse models of ochronosis have confirmed the dose relationships between HGA and ochronosis and also their modulation by p-hydroxyphenylpyruvate dioxygenase inhibition. Ochronosis cannot be fully reversed and is a key factor in influencing treatment decisions. Earlier detection of ochronosis preferably by noninvasive means is desirable. A cause-effect relationship between HGA and ochronosis is discussed. The similarity in AKU and familial hypercholesterolaemia is explored and lessons learnt. More research is needed to more fully understand the crucial nature of ochronosis.
Topics: Alkaptonuria; Animals; Cartilage; Chondrocytes; Homogentisic Acid; Humans; Mice; Ochronosis; Oxidation-Reduction; Pigmentation
PubMed: 31282009
DOI: 10.1002/jimd.12152 -
Journal of Pediatric Endocrinology &... Feb 2020Background Alkaptonuria (OMIM: 203500) is an inborn error of metabolism due to homogentisate 1,2-dioxygenase homogentisic acid 1,2 dioxygenase (HGD) enzyme deficiency....
Background Alkaptonuria (OMIM: 203500) is an inborn error of metabolism due to homogentisate 1,2-dioxygenase homogentisic acid 1,2 dioxygenase (HGD) enzyme deficiency. Due to the enzyme deficiency, homogentisic acid cannot be converted to maleylacetoacetate and it accumulates in body fluids. Increased homogentisic acid is converted to benzoquinones, the resulting benzoquinones are converted to melanin-like pigments, and these pigments are deposited in collagen - this process is called ochronosis. In patients with alkaptonuria, the urine is darkened, which is misinterpreted as hematuria, the incidences of renal stones, arthritis and cardiac valve calcification are increased, and spontaneous tendon ruptures, prostatitis and prostate stones can be encountered. The present study aimed to evaluate the HGD gene mutations in 14 patients with alkaptonuria. Methods Fourteen patients diagnosed with alkaptonuria and followed up from 1990 to 2014 were retrospectively evaluated. Their demographic, clinical and treatment-related data were retrieved from hospital files. For mutation analysis, genomic DNAs of the patients were isolated from their peripheral blood samples. Variations in the HGD gene were scanned on the HGD-mutation database (http://hgddatabase.cvtisr.sk). Results Among 14 patients, the female/male ratio was 1/1 and the median age was 9 years (range, 6-59 years). All patients were symptomatic at their first visit and the most common symptom was dark urine (71%) followed by arthralgia. Independent of the urinary homogentisic acid concentrations, patients with the presenting symptom of arthralgia were elder. Nine different mutations including p.Ser59AlafsX52, p.Gly161Arg, p.Asn219Ser, p.Gly251Asp, p.Pro274Leu, p.Arg330Ser, p.Gly372Ala, c.656_657insAATCAA and a novel mutation of p.Val316Ile were detected. All of the pediatric-age patients (n = 13) were treated with ascorbic acid at a dose of 250-1000 mg/day. Conclusions Nine different HGD gene mutations with a novel one, p.Val316Ile, were detected. The most common mutation was p.Ser59AlafsX52 for the HGD gene followed by p.Gly161Arg and p.asn219Ser, which can be considered specific to the Turkish population.
Topics: Adolescent; Adult; Alkaptonuria; Biomarkers; Child; DNA Mutational Analysis; Female; Follow-Up Studies; Hepatocyte Growth Factor; Humans; Male; Middle Aged; Mutation; Prognosis; Retrospective Studies; Turkey; Young Adult
PubMed: 31927521
DOI: 10.1515/jpem-2019-0163 -
Journal of Pediatric Endocrinology &... Jul 2022Alkaptonuria is a rare autosomal recessive genetic disorder resulting from the deficiency of homogentisate 1,2 dioxygenase (HGD), the third enzyme in the tyrosine...
OBJECTIVES
Alkaptonuria is a rare autosomal recessive genetic disorder resulting from the deficiency of homogentisate 1,2 dioxygenase (HGD), the third enzyme in the tyrosine degradation pathway. Homogentisic acid produced in excess oxidizes into ochronotic pigment polymer. Accumulation of this pigment in various tissues leads to systemic disease.
METHODS
Clinical, laboratory, molecular findings and treatment characteristics of 35 patients followed up in Ege University Pediatric Nutrition, and Metabolism Department with the diagnosis of alkaptonuria were evaluated retrospectively.
RESULTS
Twenty-four males (68.57%) and 11 females (31.42%) with a confirmed diagnosis of alkaptonuria from 32 different families were included in the study. We identified 11 different genetic variants; six of these were novel. c.1033C>T, c.676G>A, c.664G>A, c.731_734del, c.1009G>T, c.859_862delins ATAC were not previously reported in the literature. 24 (68.57%) patients only adhered to a low-protein diet in our study group. Seven (20%) patients initiated a low protein diet and NTBC therapy. Mean urinary HGA decreased by 88.7% with nitisinone. No statistical changes were detected in urinary HGA excretion with the low protein diet group.
CONCLUSIONS
In our study, alkaptonuria patients were diagnosed at different ages, from infancy to adulthood, and progressed with other systemic involvement in the follow-up. Since the initial period is asymptomatic, giving potentially effective treatment from an early age is under discussion. Raising disease awareness is very important in reducing disease mortality and morbidity rates.
Topics: Adult; Alkaptonuria; Child; Female; Follow-Up Studies; Homogentisate 1,2-Dioxygenase; Homogentisic Acid; Humans; Male; Retrospective Studies; Tyrosine
PubMed: 35671204
DOI: 10.1515/jpem-2022-0004 -
Histopathology Nov 2008Alkaptonuria is a rare, inherited defect of homogentisic acid 1,2-dioxygenase that leads to the widespread deposition of polymeric homogentisic acid, and clinical... (Review)
Review
Alkaptonuria is a rare, inherited defect of homogentisic acid 1,2-dioxygenase that leads to the widespread deposition of polymeric homogentisic acid, and clinical symptoms from degeneration of joints and the aortic valve. Pathological descriptions are few and mainly those of late-stage changes related to joint or valve failure. In this review, the macroscopic and histopathological changes in the tissues in alkaptonuria are illustrated by the detailed autopsy study of a 74-year-old female who died from disseminated ovarian carcinoma. The pathology is discussed in the context of the literature and in relation to potential pathogenic mechanisms of tissue damage. This review highlights the heterogeneity of some of the manifestations. In symptomatic patients, degenerative changes in synovial and intervertebral joints are usually well advanced, while early changes include diffuse cartilage pigmentation and chondrocyte necrosis. The initial stage of pigment deposition in the cardiovascular system may be influenced by intravascular pressure and flow disturbances, whereas more intense pigmentation affects fibrolipid components of atheromatous plaques. Pigmentation of the aortic and mitral valve cusps and valve rings is a result of intracellular and extracellular pigment deposition and is associated with calcification and clinically significant aortic stenosis.
Topics: Alkaptonuria; Aortic Valve Stenosis; Autopsy; Female; Humans; Male
PubMed: 18336562
DOI: 10.1111/j.1365-2559.2008.03000.x -
British Journal of Neurosurgery Dec 2008Alkaptonuria is a rare autosomal recessive metabolic disease that leads to the deposition of homogentisic acid. Ochronotic arthropathy is the articular manifestation of... (Review)
Review
Alkaptonuria is a rare autosomal recessive metabolic disease that leads to the deposition of homogentisic acid. Ochronotic arthropathy is the articular manifestation of alkaptonuria with the most common clinical feature being severe spondyloarthropathy. We present the case of a 58-year-old woman with back pain. Radiographs and magnetic resonance imaging (MRI) revealed characteristic features of ochronotic spondyloarthropathy. The literature regarding management of alkaptonuria is reviewed.
Topics: Alkaptonuria; Antioxidants; Ascorbic Acid; Female; Homogentisate 1,2-Dioxygenase; Homogentisic Acid; Humans; Low Back Pain; Middle Aged; Ochronosis; Spondylarthropathies
PubMed: 19085367
DOI: 10.1080/02688690802226368 -
Journal of Inherited Metabolic Disease Sep 2023Until now, only a few studies have focused on the early onset of symptoms of alkaptonuria (AKU) in the pediatric population. This prospective, longitudinal study is a...
Until now, only a few studies have focused on the early onset of symptoms of alkaptonuria (AKU) in the pediatric population. This prospective, longitudinal study is a comprehensive approach to the assessment of children with recognized AKU during childhood. The study includes data from 32 visits of 13 patients (five males, eight females; age 4-17 years) with AKU. A clinical evaluation was performed with particular attention to eye, ear, and skin pigmentation, musculoskeletal complaints, magnetic resonance imaging (MRI), and ultrasound (US) imaging abnormalities. The cognitive functioning and adaptive abilities were examined. Molecular genetic analyses were performed. The most common symptoms observed were dark urine (13/13), followed by joint pain (6/13), and dark ear wax (6/13). In 4 of 13 patients the values obtained in the KOOS-child questionnaire were below the reference values. MRI and US did not show degenerative changes in knee cartilages. One child had nephrolithiasis. Almost half of the children with AKU (5/13) presented deficits in cognitive functioning and/or adaptive abilities. The most frequent HGD variants observed in the patients were c.481G>A (p.Gly161Arg) mutation and the c.240A>T (p.His80Gln) polymorphism. The newly described allele of the HGD gene (c.948G>T, p.Val316Phe) which is potentially pathogenic was identified.
Topics: Child; Male; Female; Humans; Child, Preschool; Adolescent; Alkaptonuria; Homogentisate 1,2-Dioxygenase; Prospective Studies; Longitudinal Studies; Mutation
PubMed: 37395296
DOI: 10.1002/jimd.12647