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The Journal of the Association of... Nov 1989A case of alkaptonuria with its various sequelae in the form of ochronosis, ochronotic arthropathy, spondylitis and prostatic calculi is reported. The case is of...
A case of alkaptonuria with its various sequelae in the form of ochronosis, ochronotic arthropathy, spondylitis and prostatic calculi is reported. The case is of interest as it presented with hepatocellular failure and hepatitis B surface antigenaemia.
Topics: Alkaptonuria; Calcinosis; Humans; Intervertebral Disc; Male; Middle Aged; Radiography
PubMed: 2632541
DOI: No ID Found -
Ryoikibetsu Shokogun Shirizu 1998
Review
Topics: Alkaptonuria; Arthritis; Diagnosis, Differential; Dioxygenases; Homogentisate 1,2-Dioxygenase; Homogentisic Acid; Humans; Ochronosis; Oxygenases; Phenylalanine; Tyrosine
PubMed: 9590059
DOI: No ID Found -
Proceedings of the Royal Society of... May 1969
Topics: Adult; Alkaptonuria; Chromatography, Gas; Humans; Male; Phenylacetates
PubMed: 5770593
DOI: No ID Found -
Skeletal Radiology May 2019Alkaptonuria is a rare inborn metabolic disorder due to a mutation in the homogentisic acid oxidase enzyme (HGO) gene on chromosome 3q. As HGO is deficient in...
Alkaptonuria is a rare inborn metabolic disorder due to a mutation in the homogentisic acid oxidase enzyme (HGO) gene on chromosome 3q. As HGO is deficient in alkaptonuria patients, there is an accumulation of homogentisic acid in the blood and urine. Homogentisic acid gets deposited in the soft tissues, tendons, cartilages, large joints and intervertebral discs. Ochronosis usually affects the dorsolumbar spine and typically spares the cervical spine and sacroiliac joints. However, in this case of isolated ochronosis, we report co-existent extensive cervical spine degenerative changes and cervical vertebral fusion, which has not been described in the literature so far.
Topics: Alkaptonuria; Cervical Vertebrae; Diagnosis, Differential; Humans; Multimodal Imaging; Spinal Diseases
PubMed: 30406834
DOI: 10.1007/s00256-018-3104-4 -
Current Protein & Peptide Science 2023Alkaptonuria (AKU), a rare genetic disorder, is characterized by the accumulation of homogentisic acid (HGA) in organs, which occurs because the homogentisate... (Review)
Review
Alkaptonuria (AKU), a rare genetic disorder, is characterized by the accumulation of homogentisic acid (HGA) in organs, which occurs because the homogentisate 1,2-dioxygenase (HGD) enzyme is not functional due to gene variants. Over time, HGA oxidation and accumulation cause the formation of the ochronotic pigment, a deposit that provokes tissue degeneration and organ malfunction. Here, we report a comprehensive review of the variants so far reported, the structural studies on the molecular consequences of protein stability and interaction, and molecular simulations for pharmacological chaperones as protein rescuers. Moreover, evidence accumulated so far in alkaptonuria research will be re-proposed as the bases for a precision medicine approach in a rare disease.
Topics: Humans; Alkaptonuria; Dioxygenases; Genetic Association Studies; Homogentisate 1,2-Dioxygenase; Homogentisic Acid; Rare Diseases; Structure-Activity Relationship
PubMed: 36880186
DOI: 10.2174/1389203724666230307104135 -
Journal of Inherited Metabolic Disease Dec 2011
Topics: 4-Hydroxyphenylpyruvate Dioxygenase; Alkaptonuria; Cyclohexanones; Humans; Nitrobenzoates; Therapies, Investigational
PubMed: 21938512
DOI: 10.1007/s10545-011-9385-6 -
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 -
Annals of Nutrition & Metabolism 2022Nitisinone used in alkaptonuria (AKU) can result in keratopathy due to strongly increased tyrosine levels. (Review)
Review
INTRODUCTION
Nitisinone used in alkaptonuria (AKU) can result in keratopathy due to strongly increased tyrosine levels.
METHODS
This study aimed to investigate nutritional status and changes in plasma tyrosine and phenylalanine and urinary homogentisic acid (u-HGA) levels in 8 adult AKU patients (mean age, 56.3 ± 4.7 years) who were on tyrosine/phenylalanine-restricted diet together with 2 mg/day nitisinone.
RESULTS
The treatment period was 23.4 ± 6.9 months. Daily dietary protein intake was restricted to 0.8-1.0 g/kg/day. Daily tyrosine intake was restricted to 260-450 mg/day for females and 330-550 mg/day for males. Tyrosine/phenylalanine-free amino acid supplements accounted for an average of 56.1% of daily protein intake. The following assessments were performed: anthropometric and plasma tyrosine level measurements every 2 months; ophthalmological examination every 6 months, and nutritional laboratory analyses and measurements of plasma amino acids and u-HGA once in a year. It was targeted to keep the plasma tyrosine level <500 μmol/L. The plasma tyrosine level was <100 μmol/L before the treatment in all patients and around a mean of 582.5 ± 194.8 μmol/L during the treatment. The diet was rearranged if a plasma tyrosine level of >700 μmol/L was detected. The u-HGA level before and after the 1st year of treatment was 1,429.3 ± 1,073.4 mmol/mol creatinine and 33.6 ± 9.5 mmol/mol creatinine, respectively. None of the patients developed keratopathy or experienced weight loss and protein or micronutrient deficiency.
CONCLUSION
AKU patients should receive tyrosine/phenylalanine-restricted diet for reducing plasma tyrosine level to the safe range. Tyrosine/phenylalanine-free amino acid supplements can be safely used to enhance dietary compliance. Keratopathy and nutrient deficiency should be frequently monitored.
Topics: Adult; Alkaptonuria; Cyclohexanones; Diet; Dietary Proteins; Female; Humans; Male; Middle Aged; Nitrobenzoates; Phenylalanine; Tyrosine
PubMed: 34736252
DOI: 10.1159/000519813 -
European Journal of Medical Genetics May 2021Alkaptonuria (AKU) is an inborn error of metabolism caused by the deficiency of homogentisate 1,2-dioxygenase (HGD) as a result of a defect in the HGD gene. HGD enzyme...
Alkaptonuria (AKU) is an inborn error of metabolism caused by the deficiency of homogentisate 1,2-dioxygenase (HGD) as a result of a defect in the HGD gene. HGD enzyme deficiency results in accumulation of homogentisic acid (HGA) in the body, which in turn leads to multisystemic clinical symptoms. The present study aimed to investigate the presenting symptoms, age at diagnosis, and clinical and genetic characteristics of AKU patients followed-up in different centers in Turkey. In this cross-sectional, multicenter, descriptive study, medical records of 66 AKU patients were retrospectively evaluated. Patients' data regarding demographic, clinical and genetic characteristics were recorded. HGD database (http://hgddatabase.cvtisr.sk/) was used to identify HGD gene variants. Of the patients, 37 (56.1%) presented with isolated dark urine and 29 (43.9%) were diagnosed based on the clinical symptoms or family screening. One of these patients was on follow-up for 2 years due to Parkinsonism and was diagnosed with AKU on further analyses. Signs of ochronosis such as joint pain, low back pain and renal stones developed in childhood in 7 patients. Eight patients were diagnosed with depression via psychiatric evaluation. There were 14 (21.2%) patients operated on for ochronosis. The most frequent mutation observed in the patients was c.175delA, which was followed by c.674G > A and c.1007-2A > T mutations. Four novel mutations (c.189G > A, c.549+1G > T, c.1188+1G > A, and c.334 T > G) were identified in the patients included in the study. In addition to the known signs such as dark urine and skin pigmentation, symptoms involving different systems such as neurological findings and depression can also be encountered in AKU patients. The presence of a change in urine color needs to be questioned in patients presenting with different symptoms such as arthralgia/arthritis, renal stones or low-back pain, particularly in childhood, when skin ochronosis is not pronounced, and further examination should be performed.
Topics: Adolescent; Adult; Alkaptonuria; Child; Child, Preschool; Depression; Diagnosis, Differential; Early Diagnosis; Female; Homogentisate 1,2-Dioxygenase; Humans; Infant; Kidney Calculi; Male; Middle Aged; Mutation; Ochronosis; Phenotype; Turkey
PubMed: 33746036
DOI: 10.1016/j.ejmg.2021.104197 -
Kidney International Jun 2020
Topics: Alkaptonuria; Humans; Kidney Diseases; Urination Disorders
PubMed: 32444099
DOI: 10.1016/j.kint.2019.12.008