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Journal of Clinical Rheumatology :... Aug 2020
Topics: Alkaptonuria; Humans; Ochronosis
PubMed: 31022057
DOI: 10.1097/RHU.0000000000001044 -
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 -
The Lancet. Diabetes & Endocrinology Sep 2020
Review
Topics: Alkaptonuria; Cyclohexanones; Enzyme Inhibitors; Humans; Nitrobenzoates
PubMed: 32822593
DOI: 10.1016/S2213-8587(20)30222-9 -
Joint Bone Spine May 2020
Topics: Alkaptonuria; Chondrocalcinosis; Humans; Intervertebral Disc; Intervertebral Disc Degeneration; Intervertebral Disc Displacement
PubMed: 31988010
DOI: 10.1016/j.jbspin.2020.01.004 -
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 -
Cells Nov 2022Nitisinone (NTBC) was recently approved to treat alkaptonuria (AKU), but there is no information on its impact on oxidative stress and inflammation, which are observed...
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) by spectrophotometry; and protein carbonyls by Western blot. Our results show that NTBC had no significant effects on the tested markers except for a slight but statistically significant effect for NTBC, but not for the combination of time and NTBC, on SAA levels in SONIA2 patients. Notably, the majority of SONIA2 patients presented with SAA > 10 mg/L, and 30 patients in the control group (43.5%) and 40 patients (58.0%) in the NTBC-treated group showed persistently elevated SAA > 10 mg/L at each visit during SONIA2. Higher serum SAA correlated with lower quality of life and higher morbidity. Despite no quantitative differences in AOPP, the preliminary analysis of protein carbonyls highlighted patterns that deserve further investigation. Overall, our results suggest that NTBC cannot control the sub-clinical inflammation due to increased SAA observed in AKU, which is also a risk factor for developing secondary amyloidosis.
Topics: Humans; Alkaptonuria; Advanced Oxidation Protein Products; Quality of Life; Biomarkers; Serum Amyloid A Protein; Inflammation; Oxidative Stress
PubMed: 36429096
DOI: 10.3390/cells11223668 -
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 -
International Journal of Dermatology Jun 2022Exogenous ochronosis is a potential side effect associated with hydroquinone, and treatment is often unsatisfactory. Our study objectives were to review data on... (Review)
Review
Exogenous ochronosis is a potential side effect associated with hydroquinone, and treatment is often unsatisfactory. Our study objectives were to review data on hydroquinone-associated ochronosis to determine risk factors for patients experiencing this adverse event. On September 27, 2020 (MEDLINE/PubMed), and October 30, 2020 (Scopus and Web of Science), databases were searched for "ochronosis + hydroquinone" by both authors to reduce risk basis. PRISMA reporting guidelines were used to select 56 articles with a total of 126 patients with hydroquinone-associated ochronosis. Included articles described hydroquinone-associated ochronosis. Articles were excluded if they had irrelevant content, were non-English language text, and were non-case studies. Full text articles were assessed and recorded. Cross-tabulation analysis was performed on categorical data, and Fisher exact test was performed. Ochronosis was most often reported in middle-aged women (53.2%), of African descent (45.2%), Black races (55.5%), and Fitzpatrick skin types V-VI (52.4%). It was most frequently reported with unknown and hydroquinone concentrations greater than 4% (32.5 and 35.7% cases, respectively). Median duration of use was 5 years, with only four cases reported with courses 3 months or shorter and eight cases reported with use 1 year or less. All patients presented with facial blue-black or gray-blue macules in a reticulate, lace-like fashion. Histopathology consistently showed solar elastosis and brownish-yellow, 'banana-shaped' fibers between degenerated collagen fibers of the papillary dermis. Based on these findings, we conclude that hydroquinone in concentrations above 4% and in treatment courses longer than 3 months may be associated with new-onset ochronosis.
Topics: Alkaptonuria; Female; Humans; Hydroquinones; Middle Aged; Ochronosis
PubMed: 34486734
DOI: 10.1111/ijd.15878