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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 -
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 -
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 -
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 -
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 -
Indian Dermatology Online Journal 2022
PubMed: 36262587
DOI: 10.4103/idoj.idoj_735_21 -
JPRAS Open Dec 2021Ochronosis is a syndrome characterized by bluish black discoloration due to the deposition of polymerized products of homogentisic acid (HGA) in the connective tissues....
Ochronosis is a syndrome characterized by bluish black discoloration due to the deposition of polymerized products of homogentisic acid (HGA) in the connective tissues. The endogenous variety (alkaptonuria), is a rare autosomal recessive metabolic disorder. The disorder is manifested by deficiency of the enzyme homogentisate 1,2-dioxygenase. The characteristic of the condition is a triad of pigmentation of skin, cartilage, and sclera; ochronotic arthropathies and homogentisic aciduria (resulting in darkening of urine). More rarely, it may affect the breast. This rare and interesting case of a woman with ochronosis of both breasts and chest wall, prompted us to write this case report.
PubMed: 34381863
DOI: 10.1016/j.jpra.2021.06.005 -
Medicine Dec 2021This study aimed to determine the patient characteristics and clinical presentation of Alkaptonuria cases reported by the Biochemical Genetics Lab.An observational study... (Observational Study)
Observational Study
This study aimed to determine the patient characteristics and clinical presentation of Alkaptonuria cases reported by the Biochemical Genetics Lab.An observational study was conducted at the Biochemical Genetics Lab. Alkaptonuria patients were diagnosed based on the homogentisic acid peak in urine and their demographics and clinical data collected from to 2013 to 2019. Clinical history related to joint diseases, ochronotic presentation, and urine darkening on standing was collected.During 7 years, 21 Alkaptonuria cases were reported from BGL; mean age 19.4 ± 24.5 years (range 0.2-66 years) and male to female ratio of 2:1. Of the total, only 9 were adults (mean age, 44 ± 12 years). Most adult patients had musculoskeletal involvement, with joint pain (n = 9) and ochronotic pigmentation (n = 6), whereas all patients presented with a history of urine darkening on standing (21/21 cases).The high prevalence of musculoskeletal involvement observed in patients with albuminuria is likely to be missed by physicians unless specifically tested for in such cases.
Topics: Adolescent; Adult; Aged; Alkaptonuria; Child; Child, Preschool; Cross-Sectional Studies; Female; Humans; Infant; Joint Diseases; Male; Middle Aged; Musculoskeletal System; Ochronosis; Pakistan; Young Adult
PubMed: 34941093
DOI: 10.1097/MD.0000000000028241 -
Endocrine Regulations Jan 2023Alkaptonuria (AKU, OMIM, No. 203500) is a rare, slow-progressing, irreversible, multisystemic disease resulting from a deficiency of the homogentisate 1,2-dioxygenase...
Alkaptonuria (AKU, OMIM, No. 203500) is a rare, slow-progressing, irreversible, multisystemic disease resulting from a deficiency of the homogentisate 1,2-dioxygenase enzyme, which leads to the accumulation of homogentisic acid (HGA) and subsequent deposition as pigment in connective tissues called ochronosis. As a result, severe arthropathy of large joints and spondyloarthropathy with frequent fractures, ligament ruptures, and osteoporosis develops in AKU patients. Since 2020, the first-time treatment with nitisinone has become available in the European Union. Nitisinone significantly reduces HGA production and arrests ochronosis in AKU patients. However, blocking of the tyrosine metabolic pathway by the drug leads to tyrosine plasma and tissue concentrations increase. The nitisinone-induced hypertyrosinemia can lead to the development of corneal keratopathy, and once it develops, the treatment needs to be interrupted. A decrease in overall protein intake reduces the risk of the keratopathy during nitisinone-induced hypertyrosinemia in AKU patients. The low-protein diet is not only poorly tolerated by patients, but over longer periods, leads to a severe muscle loss and weight gain due to increased energy intake from carbohydrates and fats. Therefore, the development of novel nutritional approaches is required to prevent the adverse events due to nitisinone-induced hypertyrosinemia and the negative impact on skeletal muscle metabolism in AKU patients.
Topics: Humans; Alkaptonuria; Ochronosis; Tyrosinemias; Tyrosine; Homogentisic Acid
PubMed: 36966367
DOI: 10.2478/enr-2023-0008 -
JAAD Case Reports Jan 2022
PubMed: 34977311
DOI: 10.1016/j.jdcr.2021.10.037