- No ochronosis was seen at internal thoracic artery with alkaptonuria. [Journal Article]
- ACAsian Cardiovasc Thorac Ann 2018 Nov 11; :218492318813791
- Alkaptonuria is a rare disorder of amino acid metabolism that causes premature large joint spine arthropathy and cardiac disease. We describe a case of aortic stenosis and coronary artery disease ass...
Alkaptonuria is a rare disorder of amino acid metabolism that causes premature large joint spine arthropathy and cardiac disease. We describe a case of aortic stenosis and coronary artery disease associated with ochronosis in a 76-year-old man who underwent aortic valve replacement and coronary artery bypass grafting. Although the ochronosis was extensive, no ochronosis was seen in the internal thoracic artery which used for coronary artery bypass grafting. Ochronosis with alkaptonuria is considered to accelerate the atherosclerotic process, so the internal thoracic artery may ensure a better long-term outcome. Long-term follow-up may allow better understanding of this rare condition.
- Evaluation of the Mitra microsampling device for use with key urinary metabolites in patients with Alkaptonuria. [Journal Article]
- BBioanalysis 2018 Nov 06
- CONCLUSIONS: Volumetric absorptive microsampling was found to be highly accurate and precise. Elution methods showed good recovery and reproducibility. Dried and liquid samples compared favorably. Analyte stability was variable, presenting barriers to implementation into routine use in this context.
- Alkaptonuria-an atypical case: multi-modality imaging review. [Journal Article]
- SRSkeletal Radiol 2018 Nov 08
- 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 accum...
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.
- An update on the role of RANKL-RANK/osteoprotegerin and WNT-β-catenin signaling pathways in pediatric diseases. [Journal Article]
- WJWorld J Pediatr 2018 Oct 20
- CONCLUSIONS: The case studies taken into account for this review demonstrated that quite frequently both bone reabsorbing and bone deposition are impaired in pediatric diseases. Furthermore, for some of them, bone damage began in childhood but only manifested with age. The use of denosumab could represent a valid alternative therapeutic approach to improve bone health in children, although further studies need to be carried out.
- Homogentisic acid induces morphological and mechanical aberration of ochronotic cartilage in alkaptonuria. [Journal Article]
- JCJ Cell Physiol 2018 Oct 20
- Alkaptonuria (AKU) is a disease caused by a deficient homogentisate 1,2-dioxygenase activity leading to systemic accumulation of homogentisic acid (HGA), that forms a melanin-like polymer that progre...
Alkaptonuria (AKU) is a disease caused by a deficient homogentisate 1,2-dioxygenase activity leading to systemic accumulation of homogentisic acid (HGA), that forms a melanin-like polymer that progressively deposits onto connective tissues causing a pigmentation called "ochronosis" and tissue degeneration. The effects of AKU and ochronotic pigment on the biomechanical properties of articular cartilage need further investigation. To this aim, AKU cartilage was studied using thermal (thermogravimetry and differential scanning calorimetry) and rheological analysis. We found that AKU cartilage had a doubled mesopore radius compared to healthy cartilage. Since the mesoporous structure is the main responsible for maintaining a correct hydrostatic pressure and tissue homoeostasis, drastic changes of thermal and rheological parameters were found in AKU. In particular, AKU tissue lost its capability to enhance chondrocytes metabolism (decreased heat capacity) and hence the production of proteoglycans. A drastic increase in stiffness and decrease in dissipative and lubricant role ensued in AKU cartilage. Multiphoton and scanning electron microscopies revealed destruction of cell-matrix microstructure and disruption of the superficial layer. Such observations on AKU specimens were confirmed in HGA-treated healthy cartilage, indicating that HGA is the toxic responsible of morphological and mechanical alterations of cartilage in AKU.
- A new integrated and interactive tool applicable to inborn errors of metabolism: Application to alkaptonuria. [Journal Article]
- CBComput Biol Med 2018 Oct 05; 103:1-7
- This paper describes our experience with the development and implementation of a database for the rare disease Alkaptonuria (AKU, OMIM: 203500). AKU is an autosomal recessive disorder caused by a gen...
This paper describes our experience with the development and implementation of a database for the rare disease Alkaptonuria (AKU, OMIM: 203500). AKU is an autosomal recessive disorder caused by a gene mutation leading to the accumulation of homogentisic acid (HGA). Analogously to other rare conditions, currently there are no approved biomarkers to monitor AKU progression or severity. Although some biomarkers are under evaluation, an extensive biomarker analysis has not been undertaken in AKU yet. In order to fill this gap, we gained access to AKU-related data that we carefully processed, documented and stored in a database, which we named ApreciseKUre. We undertook a suitable statistical analysis by associating every couple of potential biomarkers to highlight significant correlations. Our database is continuously updated allowing us to find novel unpredicted correlations between AKU biomarkers and to confirm system reliability. ApreciseKUre includes data on potential biomarkers, patients' quality of life and clinical outcomes facilitating their integration and possibly allowing a Precision Medicine approach in AKU. This framework may represent an online tool that can be turned into a best practice model for other rare diseases.
- Collagenous and elastotic marginal plaques of the hand: A potential clue to the diagnosis of alkaptonuria. [Case Reports]
- JCJ Cutan Pathol 2018 Oct 07
- Collagenous and elastotic marginal plaques of the hand (CEMPH) is a rare, chronic keratoderma characterized by hyperkeratotic linear plaques located along the radial and ulnar aspects of the hands bi...
Collagenous and elastotic marginal plaques of the hand (CEMPH) is a rare, chronic keratoderma characterized by hyperkeratotic linear plaques located along the radial and ulnar aspects of the hands bilaterally. As an isolated finding, CEMPH occurs secondarily to chronic trauma and photodamage. Herein, CEMPH is described as a manifestation of alkaptonuria (AKU). In addition to keloidal collagen, ochronotic fibers and fragmented, thickened elastic fibers were observed. Additionally, mucin deposition-not previously described in this clinical context-was also identified. Given their overlapping clinicopathologic features, CEMPH due to AKU should be distinguished from the acquired variant as well as acrokeratoelastoidosis.
- Data on items of AKUSSI in Alkaptonuria collected over three years from the United Kingdom National Alkaptonuria Centre and the impact of nitisinone. [Journal Article]
- DBData Brief 2018; 20:1620-1628
- Alkaptonuria is a rare genetic disorder characterized by a high level of circulating (and urine) homogentisic acid (HGA), which contributes to ochronosis when it is deposited in connective tissue as ...
Alkaptonuria is a rare genetic disorder characterized by a high level of circulating (and urine) homogentisic acid (HGA), which contributes to ochronosis when it is deposited in connective tissue as a pigmented polymer. In an observational study carried out by National AKU Centre (NAC) in Liverpool, a total of thirty-nine AKU patients attended yearly visits in varying numbers. At each visit a mixture of clinical, joint and spinal assessments were carried out and the results calculated to yield an AKUSSI (Alkaptonuria Severity Score Index), see "Nitisinone arrests ochronosis and decreases rate of progression of Alkaptonuria: evaluation of the effect of nitisinone in the United Kingdom National Alkaptonuria Centre" (Ranganath at el., 2018). The aim of this data article is to produce visual representation of the change in the components of AKUSSI over 3 years, through radar charts. The metabolic effect of nitisinone is shown through box plots.
- Ochronosis Presenting as Methemoglobinemia. [Case Reports]
- JFJ Forensic Sci 2018 Sep 19
- Ochronosis is the blue-gray discoloration of collagen-containing tissues due to homogentisic acid (HGA) deposition, secondary to endogenous alkaptonuria or exogenous enzyme inhibition. In renal disea...
Ochronosis is the blue-gray discoloration of collagen-containing tissues due to homogentisic acid (HGA) deposition, secondary to endogenous alkaptonuria or exogenous enzyme inhibition. In renal disease, accumulation of HGA in serum can cause methemoglobinemia. A 60-year-old woman with renal disease and anemia presented with 3 days of weakness and months of gray skin discoloration. Her hemoglobin was 8.1g/dl with 24.5% methemoglobin. Despite treatment with methylene blue, exchange transfusion, and continuous renal replacement therapy, the patient died. Autopsy revealed gray discoloration and ochronotic pigment in the ribs and cartilage. Based on these findings, the patient was diagnosed with ochronosis, suggestive of alkaptonuria, complicated by methemoglobinemia. The differential diagnosis for blue-gray skin discoloration includes argyria, methemoglobinemia, and ochronosis. This patient's clinical and autopsy findings suggested alkaptonuria complicated by methemoglobinemia due to progressive renal dysfunction. Development of methemoglobinemia in the setting of chronic skin discoloration and renal failure should prompt consideration of alkaptonuria.
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- Recognition of Alkaptonuria During Mohs Micrographic Surgery. [Journal Article]
- DSDermatol Surg 2018 Sep 10