-
Clinical Medicine Insights. Arthritis... 2023Ankylosing spondylitis is the most common type of seronegative inflammatory spondyloarthropathy often presenting with low back or neck pain, stiffness, kyphosis and... (Review)
Review
Ankylosing spondylitis is the most common type of seronegative inflammatory spondyloarthropathy often presenting with low back or neck pain, stiffness, kyphosis and fractures that are initially missed on presentation; however, there are other spondyloarthropathies that may present similarly making it a challenge to establish the correct diagnosis. Here, we will highlight the similarities and unique features of the epidemiology, pathophysiology, presentation, radiographic findings, and management of seronegative inflammatory and metabolic spondyloarthropathies as they affect the axial skeleton and mimic ankylosing spondylitis. Seronegative inflammatory spondyloarthropathies such as psoriatic arthritis, reactive arthritis, noninflammatory spondyloarthropathies such as diffuse idiopathic skeletal hyperostosis, and ochronotic arthritis resulting from alkaptonuria can affect the axial skeleton and present with symptoms similar those of ankylosing spondylitis. These similarities can create a challenge for providers as they attempt to identify a patient's condition. However, there are characteristic radiographic findings and laboratory tests that may help in the differential diagnosis. Axial presentations of seronegative inflammatory, non-inflammatory, and metabolic spondyloarthropathies occur more often than previously thought. Identification of their associated symptoms and radiographic findings are imperative to effectively diagnose and properly manage patients with these diseases.
PubMed: 37533960
DOI: 10.1177/11795441231186822 -
International Journal of Surgery Case... Nov 2022Alkaptonuria is an autosomal recessive disease due to lack of the enzyme homogentisic acid oxidase. Homogentisic Acid (HA) is in the metabolism pathway of phenylalanine....
INTRODUCTION AND IMPORTANCE
Alkaptonuria is an autosomal recessive disease due to lack of the enzyme homogentisic acid oxidase. Homogentisic Acid (HA) is in the metabolism pathway of phenylalanine. The musculoskeletal symptomatology begins generally in the fourth decade. We reported the case of a 50 year old man who had ochronotic arthropathy and degenerative changes in knee joint and who was treated with total knee arthroplasty.
CASE PRESENTATION
A 50 year old man presented to our outpatient clinic with bilateral knee pain. Pain was exaggerated with effort and decreases with rest. The patient had no medical history. While performing the total knee arhtroplasty for our patient, we discovered intraoperatively the black coloration of the articular cartilage of the knee. At 6 months follow up, the patient was satisfied with the result with no knee pain in the treated knee. Range of knee motion was 0° in total extension to 100° of flexion. Radiological control showed a stable prosthesis not affected by ochronose.
CLINICAL DISCUSSION
Alkaptonuria is caused by lack of the enzyme homogentisic acid oxidase, is a rare autosomal recessive disease leading accumulation of homogentisic acid in connective tissue. This leads to many manifestations such as urinary, cardiac, dermatologic, ophthalmologic or musculoskeletal symptoms. Deposit of Homogentisic acid in articular cartilage gives the characteristic black or dark brown pigmentation of the cartilage. Its clinical traduction is symptomatology of degenerative modifications in multiples joints such as knee, shoulder or hip beside the lumbar spine arthrosis.
CONCLUSION
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.
PubMed: 36327861
DOI: 10.1016/j.ijscr.2022.107682 -
Metabolites Sep 2022This 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... (Review)
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 tyrosine. Nitisinone is used to treat the rare disease hereditary tyrosinaemia type 1 where the last enzyme in the breakdown of tyrosine, fumarylacetoacetase is deficient. Nitisinone is also used to treat patients with alkaptonuria where the enzyme homogentisic acid oxidase is deficient. Articles in this issue discuss metabolites of tyrosine catabolism in healthy patients and those with alkaptonuria.
PubMed: 36295804
DOI: 10.3390/metabo12100902 -
BMJ Case Reports Feb 2021Alkaptonuria is a rare genetic disorder resulting in abnormality of tyrosine metabolism. It is one of the Garrod's tetrad of 'inborn errors of metabolism' proposed to...
Alkaptonuria is a rare genetic disorder resulting in abnormality of tyrosine metabolism. It is one of the Garrod's tetrad of 'inborn errors of metabolism' proposed to have Mendelian recessive inheritance. The disorder is characterised by deposition of homogentisic acid leading to ochronosis and ochronotic osteoarthropathy; however, blackish discoloration of urine is the only childhood manifestation. Other manifestations present only after third decade. A 13-year-old boy presented to paediatric nephrology clinic with blackish discolouration of urine since infancy. Examination revealed bluish black discolouration of bilateral sclera and ear cartilage; however, he had no symptoms of ochronotic osteoarthropathy. Genetic test pointed towards alkaptonuria. Currently, he is on regular follow-up and is being treated with vitamin C to delay the progression of the disease. Early diagnosis with appropriate intervention delays the onset of complications and preserves the quality of life of the patient.
Topics: Adolescent; Alkaptonuria; Antioxidants; Ascorbic Acid; Disease Progression; Early Diagnosis; Humans; Male; Ochronosis; Sclera
PubMed: 33541951
DOI: 10.1136/bcr-2020-240147 -
Aorta (Stamford, Conn.) Aug 2021A-76-year old male with a past history of alkaptonuria with ochronosis (homogentisic acid deposition in tissues) had symptomatic aortic stenosis. Surgical replacement of...
A-76-year old male with a past history of alkaptonuria with ochronosis (homogentisic acid deposition in tissues) had symptomatic aortic stenosis. Surgical replacement of the valve was undertaken, and he was noted to have a severely pigmented and porcelain aorta.
PubMed: 34715699
DOI: 10.1055/s-0041-1729916 -
Neuroscience and Biobehavioral Reviews Jan 2022Neurometabolic diseases (NMDs) are typically caused by genetic abnormalities affecting enzyme functions, which in turn interfere with normal development and activity of... (Review)
Review
Neurometabolic diseases (NMDs) are typically caused by genetic abnormalities affecting enzyme functions, which in turn interfere with normal development and activity of the nervous system. Although the individual disorders are rare, NMDs are collectively relatively common and often lead to lifelong difficulties and high societal costs. Neuropsychiatric manifestations, including ADHD symptoms, are prominent in many NMDs, also when the primary biochemical defect originates in cells and tissues outside the nervous system. ADHD symptoms have been described in phenylketonuria, tyrosinemias, alkaptonuria, succinic semialdehyde dehydrogenase deficiency, X-linked ichthyosis, maple syrup urine disease, and several mitochondrial disorders, but are probably present in many other NMDs and may pose diagnostic and therapeutic challenges. Here we review current literature linking NMDs with ADHD symptoms. We cite emerging evidence that many NMDs converge on common neurochemical mechanisms that interfere with monoamine neurotransmitter synthesis, transport, metabolism, or receptor functions, mechanisms that are also considered central in ADHD pathophysiology and treatment. Finally, we discuss the therapeutic implications of these findings and propose a path forward to increase our understanding of these relationships.
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Depressants; Humans
PubMed: 34774900
DOI: 10.1016/j.neubiorev.2021.11.012 -
Clinical Case Reports Apr 2022Blue discoloration of the skin and cartilage, or ochronosis, is a rare physical examination finding. We present two cases of childhood onset ochronosis, one exogenous...
Blue discoloration of the skin and cartilage, or ochronosis, is a rare physical examination finding. We present two cases of childhood onset ochronosis, one exogenous and one endogenous in etiology. The first was caused by minocycline use for severe acne, and the second was caused by congenital alkaptonuria.
PubMed: 35441025
DOI: 10.1002/ccr3.5717 -
Biomedicines Sep 2023Endogenous ochronosis, also known as alkaptonuria, is a rare disease known for its bluish-black discoloration of the skin, sclerae, and pinnae, as well as urine that...
Endogenous ochronosis, also known as alkaptonuria, is a rare disease known for its bluish-black discoloration of the skin, sclerae, and pinnae, as well as urine that turns black upon standing. Though rarely fatal, joint degradation is a common sequela, and many patients require multiple large joint arthroplasties throughout their lifetime. Though many aspects of the pathophysiological mechanisms of the disease have been described, questions remain, such as how the initiation of ochronotic pigmentation is prompted and the specific circumstances that make some tissues more resistant to pigmentation-related damage than others. In this report, we present the case of an 83-year-old female previously diagnosed with alkaptonuria including high-quality arthroscopic images displaying the fraying of articular cartilage. We also offer a summary of the latest literature on the pathophysiological mechanisms of the disease, including cellular-level changes observed in ochronotic chondrocytes, biochemical and mechanical alterations to the cartilaginous extracellular matrix, and patterns of pigmentation and joint degradation observed in humans and mice models. With these, we present an overview of the mechanisms of ochronotic chondropathy and joint degradation as the processes are currently understood. While alkaptonuria itself is rare, it has been termed a "fundamental disease," implying that its study and greater understanding have the potential to lead to insights in skeletal biology in general, as well as more common pathologies such as osteoarthritis and their potential treatment mechanisms.
PubMed: 37892999
DOI: 10.3390/biomedicines11102625 -
Journal of Industrial Microbiology &... Jul 2022Pyomelanin is a brown-black phenolic polymer and results from the oxidation of homogentisic acid (HGA) in the L-tyrosine pathway. As part of the research for natural and... (Review)
Review
Pyomelanin is a brown-black phenolic polymer and results from the oxidation of homogentisic acid (HGA) in the L-tyrosine pathway. As part of the research for natural and active ingredients issued from realistic bioprocesses, this work re-evaluates the HGA pigment and makes an updated inventory of its syntheses, microbial pathways, and properties, with tracks and recent advances for its large-scale production. The mechanism of the HGA polymerization is also well documented. In alkaptonuria, pyomelanin formation leads to connective tissue damage and arthritis, most probably due to the ROS issued from HGA oxidation. While UV radiation on human melanin may generate degradation products, pyomelanin is not photodegradable, is hyperthermostable, and has other properties better than L-Dopa melanin. This review aims to raise awareness about the potential of this pigment for various applications, not only for skin coloring and protection but also for other cells, materials, and as a promising (semi)conductor for bioelectronics and energy.
Topics: Homogentisic Acid; Humans; Melanins; Pigmentation; Tyrosine
PubMed: 35482661
DOI: 10.1093/jimb/kuac013 -
Orphanet Journal of Rare Diseases Aug 2021Alkaptonuria (AKU, OMIM 203500) is a rare congenital disorder caused by a deficiency of the enzyme homogentisate-1,2,-dioxygenase. The long-term consequences of AKU are...
Alkaptonuria (AKU, OMIM 203500) is a rare congenital disorder caused by a deficiency of the enzyme homogentisate-1,2,-dioxygenase. The long-term consequences of AKU are joint problems, cardiac valve abnormalities and renal problems. Landmark intervention studies with nitisinone 10 mg daily, suppressing an upstream enzyme activity, demonstrated its beneficial effects in AKU patients with established complications, which usually start to develop in the fourth decade. Lower dose of nitisinone in the range of 0.2-2 mg daily will already reduce urinary homogentisic acid (uHGA) excretion by > 90%, which may prevent AKU-related complications earlier in the course of the disease while limiting the possibility of side-effects related to the increase of plasma tyrosine levels caused by nitisinone. Future preventive studies should establish the lowest possible dose for an individual patient, the best age to start treatment and also collect evidence to which level uHGA excretion should be reduced to prevent complications.
Topics: Alkaptonuria; Cyclohexanones; Humans; Nitrobenzoates; Tyrosine
PubMed: 34344451
DOI: 10.1186/s13023-021-01977-0