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Metabolites Sep 2022Changes in the phenylalanine (PHE)/tyrosine (TYR) pathway metabolites before and during homogentisic acid (HGA)-lowering by nitisinone in the Suitability of Nitisinone...
Changes in the phenylalanine (PHE)/tyrosine (TYR) pathway metabolites before and during homogentisic acid (HGA)-lowering by nitisinone in the Suitability of Nitisinone in Alkaptonuria (AKU) 2 (SONIA 2) study enabled the magnitude of the flux in the pathway to be examined. SONIA 2 was a 48-month randomised, open-label, evaluator-blinded, parallel-group study performed in the UK, France and Slovakia recruiting patients with confirmed AKU to receive either 10 mg nitisinone or no treatment. Site visits were performed at 3 months and yearly thereafter. Results from history, photographs of eyes/ears, whole body scintigraphy, echocardiography and abdomen/pelvis ultrasonography were combined to produce the Alkaptonuria Severity Score Index (cAKUSSI). PHE, TYR, hydroxyphenylpyruvate (HPPA), hydroxyphenyllactate (HPLA) and HGA metabolites were analysed by liquid chromatography/tandem mass spectrometry in 24 h urine and serum samples collected before and during nitisinone. Serum metabolites were corrected for total body water (TBW), and the sum of 24 h urine plus total body water metabolites of PHE, TYR, HPPA, HPLA and HGA were determined. The sum of urine metabolites (PHE, TYR, HPPA, HPLA and HGA) were similar pre- and peri-nitisinone. The sum of TBW metabolites and sum TBW + URINE metabolites were significantly higher peri-nitisinone (p < 0.001 for both) compared with pre-nitisinone baseline. Significantly higher concentrations of metabolites from the tyrosine metabolic pathway were observed during treatment with nitisinone. Arguments for unmasking of the ochronotic pathway and biliary elimination of HGA are put forward.
PubMed: 36295821
DOI: 10.3390/metabo12100920 -
Anais Brasileiros de Dermatologia 2023
Topics: Humans; Carbon Dioxide; Ochronosis; Alkaptonuria; Lasers, Gas; Treatment Outcome
PubMed: 36273949
DOI: 10.1016/j.abd.2021.08.013 -
Indian Dermatology Online Journal 2022
PubMed: 36262587
DOI: 10.4103/idoj.idoj_735_21 -
Journal of Medical Case Reports Oct 2022We present this report of a new ophthalmic finding in a patient with ochronosis.
BACKGROUND
We present this report of a new ophthalmic finding in a patient with ochronosis.
CASE PRESENTATION
An 85-year-old Caucasian male patient with bilateral dark temporal and nasal pigmentation of conjunctiva and sclera was referred to our hospital owing to low visual acuity. On biomicroscopic examination, bilateral horizontal Descemet's membrane folds were observed. Corneal tomography revealed irregular and asymmetric "against-the-rule" astigmatism in both eyes. Anterior segment optical coherence tomography demonstrated numerous central Descemet's without edema or other corneal structure alterations.
CONCLUSION
This is the first report of Descemet's membrane folds in ochronosis. These corneal findings suggest that the accumulation of homogentisic acid in the sclera leads to thickening and stiffness of this region. These alterations could remarkably decrease visual acuity owing to topographic corneal curvature alterations, especially in elderly patients.
Topics: Aged; Aged, 80 and over; Cornea; Descemet Membrane; Homogentisic Acid; Humans; Male; Ochronosis; Visual Acuity
PubMed: 36183119
DOI: 10.1186/s13256-022-03599-x -
Rheumatology International Dec 2022Alkaptonuria is a disease often forgotten because of its rarity. Its pathogenic mechanism is the deficiency of one of the enzymes of the tyrosine degradation... (Review)
Review
Alkaptonuria is a disease often forgotten because of its rarity. Its pathogenic mechanism is the deficiency of one of the enzymes of the tyrosine degradation pathway-homogentisate-1, 2-dioxygenase, which sequelae is accumulation and deposition of its metabolite homogentisic acid in connective tissues and urine. Alkaptonuria presents as a clinical triad-darkening urine upon prolonged exposure to air, pigmentation of connective tissues and debilitating arthropathy. We present a case report of a 67-year old patient with alkaptonuria who presented with the clinical triad, but was mistakenly diagnosed as having ankylosing spondylitis in the past. Currently there is no treatment for the disease hence the management strategy was focused on symptoms control with analgesics, physical therapy, dietary modification, vitamin C supplementation, and joint arthroplasty. Alkaptonuria's clinical features are extensively described in the literature and despite the fact that it is a rare disease, due to the similar radiographic changes with spondyloarthropathies, it should be included in the differential diagnosis in young patients presenting with severe joint involvement. Early recognition of the disease is necessary since its natural evolution is joint destruction leading to significant reduction in the quality of life. Alkaptonuria's articular features in the spine and peripheral tissues are well described using the classical imaging techniques. Musculoskeletal ultrasonography shows a characteristic set of findings in the soft tissues, including synovium, cartilage, tendons and entheses.
Topics: Aged; Alkaptonuria; Ascorbic Acid; Cartilage Diseases; Dioxygenases; Homogentisic Acid; Humans; Joint Diseases; Ochronosis; Osteoarthritis; Quality of Life; Spondylarthropathies; Tyrosine
PubMed: 36053307
DOI: 10.1007/s00296-022-05191-4 -
Annals of Medicine and Surgery (2012) Aug 2022Alkaptonuria is a rare hereditary disease with a defective enzyme that results in increased homogentisic acid levels in the body. Homogentisic acid accumulates in...
Alkaptonuria is a rare hereditary disease with a defective enzyme that results in increased homogentisic acid levels in the body. Homogentisic acid accumulates in multiple body parts and initializes tissue damage. Clinical manifestations such as pigmentation of the skin areas and joint destruction result in ochronosis. Nitisinone decreases serum and urinary homogentisic acid levels, improving morbidity by preventing and slowing the progression of alkaptonuria. Nitisinone-induced hypertyrosinemia causes keratopathy and mental ill effects, which can be managed by diet restriction and regular check-ups. A personalized approach is required for treatment by nitisinone. Low-dose oral nitisinone is associated with overall good results and a better safety profile.
PubMed: 36045846
DOI: 10.1016/j.amsu.2022.104340 -
Ophthalmology Nov 2022
Topics: Humans; Alkaptonuria; Ochronosis
PubMed: 35773072
DOI: 10.1016/j.ophtha.2022.03.012 -
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 -
Acta Bio-medica : Atenei Parmensis Jun 2022Alkaptonuria is a rare disease characterized by the accumulation of homogentisic acid (HGA). Over time, these patients may develop disabling ochronotic arthropathy. We...
BACKGROUND AND OBJECTIVE
Alkaptonuria is a rare disease characterized by the accumulation of homogentisic acid (HGA). Over time, these patients may develop disabling ochronotic arthropathy. We present 2 cases of patients with end-stage arthropathy treated with total knee arthroplasty (TKA).
METHODS
Both patients complained of disabling knee pain and reported limited walking distance (200-300 m). One had a history of osteotomy for medial knee arthtritis and ignored his underlying condition. The other presented with valgus gonoarthrosis and diagnosis of alkaptonuria.
RESULTS
Intraoperatively, the characteristic dark-blue color in the joint was observed. Both patients evolved favorably after TKA with excellent results according to the Knee Society Scores (KSS) at three years of follow-up.
CONCLUSION
We believe TKA is the right treatment for patients with end-stage disease because it offers considerable relief from pain and allows patients to recover function.
Topics: Alkaptonuria; Arthroplasty, Replacement, Knee; Humans; Joint Diseases; Ochronosis; Pain
PubMed: 35671127
DOI: 10.23750/abm.v92iS1.10439 -
La Revue de Medecine Interne Nov 2022Ochronosis, also known as alkaptonuria, is a rare autosomal recessive disease. It is caused by a lack of homogentisic acid oxidase, which causes homogentisic acid...
INTRODUCTION
Ochronosis, also known as alkaptonuria, is a rare autosomal recessive disease. It is caused by a lack of homogentisic acid oxidase, which causes homogentisic acid deposition in the tissues.
CASE REPORT
We report a 69-year-old patient who presented with chronic mechanical low back and radicular pain. The clinical examination revealed lumbar lordosis loss, lumbar spinal stiffness, and knee joint limitations of range of motion. On an extra-articular level, the pavilions of the ears and the internal angles of the eyes had a bluish color. Extensive lumbar disc calcifications, vacuum discal phenomenon and osteophytic bridges were demonstrated on standard radiographs of the spine. Clinical and radiographic criteria were used to make the diagnosis of ochronosis.
CONCLUSION
Alkaptonuria is a degenerative arthropathy that leads to reduction of functional ability. The use of molecular analysis and genetic research is useful.
Topics: Humans; Aged; Ochronosis; Alkaptonuria; Homogentisic Acid; Radiography; Knee Joint
PubMed: 35659777
DOI: 10.1016/j.revmed.2022.05.003