- Ochronotic arthropathy of bilateral hip joints: A case report. [Case Reports]
- CONCLUSIONS: Ochronosis is an unusual diagnosis for a patient who presents with typical hip arthritis. Thus, unless meticulous history taking and advanced laboratory tests, the diagnosis can easily be missed by surgeons.
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- Total knee arthroplasty and physical therapy for arthropathy in alkaptonuria: A 4-year follow-up case report. [Case Reports]
- CONCLUSIONS: It is rare that the knee pain is diagnosed as alkaptonuria. After total knee arthroplasty and physical therapy, the patient had a good outcome. This case provides experience for the diagnosis and treatment of alkaptonuria-related knee arthritis.
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- Case report: Thoracolumbar spinal stenosis associated with alkaptonuria. [Case Reports]
- CONCLUSIONS: This case is the first report of thoracolumbar spinal stenosis associated with alkaptonuria involving the spine.
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- Alkaptonuria: A rare cause of severe aortic stenosis treated by transcatheter aortic valve replacement. [Journal Article]Rev Port Cardiol. 2023 Jan 03 [Online ahead of print]RP
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- Bacterial quality of urinary tract in patients with alkaptonuria. [Journal Article]Am J Med Sci. 2023 Jan 03 [Online ahead of print]AJ
- CONCLUSIONS: The results deduced that males show symptoms of arthritis early and more severely than females and by this it appears that there is an association between these symptoms and the percentage of bacterial infection in males that requires more accurate diagnosis and treatment to clarify such relationship. In the current study, males (patients, carriers, and controls) were more likely to have bacterial infections than females (64% vs. 36%). The 16 and 2 bacterial isolates, detected in 7 males and 2 females AKU patients, respectively revealed that male AKU patients had a 2.3-fold greater rate of bacterial infection than female AKU patients. Therefore, further studies are warranted to investigate if there's any relationship between higher incidence of bacterial infections and development of AKU-related clinical symptoms in the male population.
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- Clinical development innovation in rare diseases: overcoming barriers to successful delivery of a randomised clinical trial in alkaptonuria-a mini-review. [Review]
- Alkaptonuria is a rare inherited disorder for which there was no disease-modifying treatment. In order to develop a successful approved therapy of AKU multiple barriers had to be overcome. These included activities before the conduct of the study including deciding on the drug therapy, the dose of the drug to be used, clarify the nature of the disease, develop outcome measures likely to yield a p…
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- Dilemmas in the diagnosis and management of osteoporosis in a patient with alkaptonuria: Successful treatment with teriparatide. [Case Reports]
- Management of osteoporosis in patients with alkaptonuria can be challenging. This is the first case report confirming the effectiveness of teriparatide following zoledronic acid therapy in treating osteoporosis and preventing fragility fractures in a patient with alkaptonuria.
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- Untargeted NMR Metabolomics Reveals Alternative Biomarkers and Pathways in Alkaptonuria. [Journal Article]
- Alkaptonuria (AKU) is an ultra-rare metabolic disease caused by the accumulation of homogentisic acid (HGA), an intermediate product of phenylalanine and tyrosine degradation. AKU patients carry variants within the gene coding for homogentisate-1,2-dioxygenase (HGD), which are responsible for reducing the enzyme catalytic activity and the consequent accumulation of HGA and formation of a dark pig…
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- Effects of Nitisinone on Oxidative and Inflammatory Markers in Alkaptonuria: Results from SONIA1 and SONIA2 Studies. [Journal Article]
- Nitisinone (NTBC) was recently approved to treat alkaptonuria (AKU), but there is no information on its impact on oxidative stress and inflammation, which are observed in AKU. Therefore, serum samples collected during the clinical studies SONIA1 (40 AKU patients) and SONIA2 (138 AKU patients) were tested for Serum Amyloid A (SAA), CRP and IL-8 by ELISA; Advanced Oxidation Protein Products (AOPP) …
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- A robust bacterial high-throughput screening system to evaluate single nucleotide polymorphisms of human homogentisate 1,2-dioxygenase in the context of alkaptonuria. [Journal Article]
- Alkaptonuria (AKU) is a rare inborn error of metabolism caused by a defective homogentisate 1,2-dioxygenase (HGD), an enzyme involved in the tyrosine degradation pathway. Loss of HGD function leads to the accumulation of homogentisic acid (HGA) in connective body tissues in a process called ochronosis, which results on the long term in an early-onset and severe osteoarthropathy. HGD's quaternary …
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- StatPearls: Ocular Manifestations Of Alkaptonuria [BOOK]StatPearls. StatPearls Publishing: Treasure Island (FL)BOOK
- Alkaptonuria is a rare autosomal recessive disorder that arises from a mutation of the homogentisate 1,2-dioxygenase (HGD) gene, resulting in a deficiency of the enzyme HGD.[1] This enzyme plays a role in the phenylalanine and tyrosine degradation pathways by catabolizing the tyrosine intermediate metabolite homogentisic acid (HGA) into maleylacetoacetic acid (Figure 1).[2] Deficiency of the HGD …
- Minocycline induced discoloration of the aortic intima and valve: A case report. [Case Reports]J Card Surg. 2022 Dec; 37(12):5548-5550.JC
- CONCLUSIONS: Given the rarity of this case, descriptions of cardiovascular ochronosis cases secondary to minocycline use are imperative in ensuring that it is on the differential diagnosis when identified by others in future cases. Additional care must be taken intraoperatively to ensure that the correct anatomy is identified as discoloration hinders visualization of the anatomy potentially resulting in unintentional consequences such as heart block or perivalvular leak as traditional visual cues for suture placement are distorted.
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- Alkaptunuria; a case report. [Case Reports]Int J Surg Case Rep. 2022 Nov; 100:107682.IJ
- CONCLUSIONS: Alkapyonuria is a very rare condition. Revealed by its orthopedic features is exceptionally. The patients, generally, need articulations replacement and the illness have no effect on its prognosis.
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- Analysis of the Phenotype Differences in Siblings with Alkaptonuria. [Journal Article]
- Alkaptonuria (AKU) is a rare autosomal recessive disorder caused by mutations within a gene coding for homogentisate 1,2-dioxygenase (HGD). To date, 251 different variants of this gene have been reported. The metabolic disorder in AKU leads to the accumulation of homogentisic acid (HGA), resulting in ochronosis (pigmentation of the connective tissues) and severe ochronotic spondylo-arthropathy, w…
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- Comprehensive Biotransformation Analysis of Phenylalanine-Tyrosine Metabolism Reveals Alternative Routes of Metabolite Clearance in Nitisinone-Treated Alkaptonuria. [Journal Article]
- Metabolomic analyses in alkaptonuria (AKU) have recently revealed alternative pathways in phenylalanine-tyrosine (phe-tyr) metabolism from biotransformation of homogentisic acid (HGA), the active molecule in this disease. The aim of this research was to study the phe-tyr metabolic pathway and whether the metabolites upstream of HGA, increased in nitisinone-treated patients, also undergo phase 1 a…
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- Revisiting Quantification of Phenylalanine/Tyrosine Flux in the Ochronotic Pathway during Long-Term Nitisinone Treatment of Alkaptonuria. [Journal Article]
- 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 Slovaki…
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- The Discovery of the Mode of Action of Nitisinone. [Review]
- This review briefly discusses the discovery of the mode of action of the triketone herbicide, 2-(2-nitro-4-trifluormethylbenzoyl)-1,3-cyclohexanedione and its use as a drug Nitisinone for the treatment of inborn errors of tyrosine metabolism. Nitisinone is a potent reversible tight-binding inhibitor of the enzyme 4-hydroxyphenylpyruvate dioxygenase, involved in the catabolism of the amino acid ty…
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- Radiological evolution of spinal disease in alkaptonuria and the effect of nitisinone. [Randomized Controlled Trial]
- CONCLUSIONS: The present study shows a relatively slow but significant worsening of radiographic features in patients with AKU over 4 years. Our results demonstrate a modest beneficial effect of 10 mg/day of nitisinone on the slowly progressing spondylosis in AKU during the relatively limited follow-up time.
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- [Alkaptonuria: Response to low-dose nitisinone in two patients with a new mutation]. [Case Reports]Med Clin (Barc). 2022 12 23; 159(12):604-605.MC
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- Descemet's membrane folds in ochronosis: a case report. [Case Reports]
- CONCLUSIONS: 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.
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- Determinants of tyrosinaemia during nitisinone therapy in alkaptonuria. [Journal Article]
- Nitisinone (NIT) produces inevitable but varying degree of tyrosinaemia. However, the understanding of the dynamic adaptive relationships within the tyrosine catabolic pathway has not been investigated fully. The objective of the study was to assess the contribution of protein intake, serum NIT (sNIT) and tyrosine pathway metabolites to nitisinone-induced tyrosinaemia in alkaptonuria (AKU). Sampl…
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- One-stage revision arthroplasty in a patient with ochronotic arthropathy accompanied by joint infection: A case report. [Case Reports]
- CONCLUSIONS: OcA accompanied by joint infection is rare. One-stage revision arthroplasty may be a treatment option for this disease.
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- HGDiscovery: An online tool providing functional and phenotypic information on novel variants of homogentisate 1,2- dioxigenase. [Journal Article]
- Alkaptonuria (AKU), a rare genetic disorder, is characterized by the accumulation of homogentisic acid (HGA) in the body. Affected individuals lack functional levels of an enzyme required to breakdown HGA. Mutations in the homogentisate 1,2-dioxygenase (HGD) gene cause AKU and they are responsible for deficient levels of functional HGD, which, in turn, leads to excess levels of HGA. Although HGA …
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- Ochronotic arthropathy in the context of spondyloarthritis differential diagnosis: a case-based review. [Case Reports]
- 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 a…
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- Adequacy of nitisinone for the management of alkaptonuria. [Journal Article]
- 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 mor…
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- Comparing the Phenylalanine/Tyrosine Pathway and Related Factors between Keratopathy and No-Keratopathy Groups as Well as between Genders in Alkaptonuria during Nitisinone Treatment. [Journal Article]
- Nitisinone (NIT) causes tyrosinaemia and corneal keratopathy (KP), especially in men. However, the adaptation within the phenylalanine (PHE)/tyrosine (TYR) catabolic pathway during KP is not understood. The objective of this study is to assess potential differences in the PHE/TYR pathway during KP and the influence of gender in NIT-induced tyrosinaemia in alkaptonuria (AKU). Samples of serum and …
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- StatPearls: Alkaptonuria [BOOK]StatPearls. StatPearls Publishing: Treasure Island (FL)BOOK
- Alkaptonuria is one of a rare autosomal recessive genetic disorder, which results from the deficiency of homogentisate 1,2 dioxygenase (HGD). HGD gene is expressed in the liver, kidney, prostate, small intestine, and colon.[1] This enzyme plays a role in the metabolism of tyrosine that converts homogentisic acid (HGA) into malate and acetoacetate. In the absence of HGD, homogentisic acid produced…
- StatPearls: Ochronosis [BOOK]StatPearls. StatPearls Publishing: Treasure Island (FL)BOOK
- Ochronosis is named for the reddish-brown hue of tissue termed "ochre-like" that was first described by a young physician named Archibald Garrod in the early-19th century. In what he called an "inborn error of metabolism," Archibald Garrod changed history when he coined that term for the obscure "black urine" disease, alkaptonuria. He proposed that ochronosis was due to deposition of a phenolic c…
- Method development and validation for analysis of phenylalanine, 4-hydroxyphenyllactic acid and 4-hydroxyphenylpyruvic acid in serum and urine. [Journal Article]
- Alkaptonuria (AKU) is a rare debilitating autosomal recessive disorder of tyrosine (TYR) metabolism which results in a deficiency of the enzyme homogentisate 1,2-dioxygenase activity. Several studies have reported the metabolic changes in homogentisic acid (HGA) concentrations and subsequent deposition of an ochronotic pigment in connective tissues, especially cartilage. Treatment with nitisinone…
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