A black heart: Aortic valve ochronosis secondary to alkaptonuria causing aortic stenosis

Vo, Tovi; Edwards, James

doi:10.1111/jocs.15272

Cited by 4 publications

(6 citation statements)

References 11 publications

(31 reference statements)

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“…As a result of less pigmentation in the venous circulation compared with the arterial circulation, continuous mechanical stress and high pressure may also play an important role in the development of ochronosis. 3 The ochronotic pigment in the aortic valve may stimulate dystrophic calcification and fibrosis, which leads to aortic valve stenosis. 1 Currently there is no successful treatment of alkaptonuria, but the prognosis is relatively good.…”

Section: Discussionmentioning

confidence: 99%

Black Aortic Valve: Incidental Finding of Alkaptonuria

Putz

Keyser

et al. 2021

Thorac Cardiovasc Surg Rep

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Background Alkaptonuria is a rare autosomal recessive genetic disorder of tyrosine metabolism, which results in accumulation of homogentisic acid in various tissues, including the cardiovascular system. Case Description We report on a 64-year-old man with mixed aortic valve disease who underwent conventional aortic valve replacement. Intraoperative aortotomy revealed black pigmentation of the intima of the ascending aorta and the aortic valve was observed with thickened and calcified dark black leaflets. Histopathological diagnosis of ochronosis of the aortic valve was made. Conclusion Despite several previous signs and symptoms, the diagnosis of alkaptonuria was not established until aortic valve replacement.

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Section: Discussionmentioning

confidence: 99%

Black Aortic Valve: Incidental Finding of Alkaptonuria

Putz

Keyser

et al. 2021

Thorac Cardiovasc Surg Rep

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“…The most common is aortic ochronosis that causes aortic stenosis and requires surgical treatment. The pulmonary and tricuspid valves are the subsequent rarely afflicted, followed by the mitral valve [ 21 ]. Certain patients have indeed reported involvement of the aortic, sternal, and coronary arteries.…”

Section: Introductionmentioning

confidence: 99%

Identification of Potential Inhibitors for the Treatment of Alkaptonuria Using an Integrated In Silico Computational Strategy

et al. 2023

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Alkaptonuria (AKU) is a rare genetic autosomal recessive disorder characterized by elevated serum levels of homogentisic acid (HGA). In this disease, tyrosine metabolism is interrupted because of the alterations in homogentisate dioxygenase (HGD) gene. The patient suffers from ochronosis, fractures, and tendon ruptures. To date, no medicine has been approved for the treatment of AKU. However, physiotherapy and strong painkillers are administered to help mitigate the condition. Recently, nitisinone, an FDA-approved drug for type 1 tyrosinemia, has been given to AKU patients in some countries and has shown encouraging results in reducing the disease progression. However, this drug is not the targeted treatment for AKU, and causes keratopathy. Therefore, the foremost aim of this study is the identification of potent and druggable inhibitors of AKU with no or minimal side effects by targeting 4-hydroxyphenylpyruvate dioxygenase. To achieve our goal, we have performed computational modelling using BioSolveIT suit. The library of ligands for molecular docking was acquired by fragment replacement of reference molecules by ReCore. Subsequently, the hits were screened on the basis of estimated affinities, and their pharmacokinetic properties were evaluated using SwissADME. Afterward, the interactions between target and ligands were investigated using Discovery Studio. Ultimately, compounds c and f were identified as potent inhibitors of 4-hydroxyphenylpyruvate dioxygenase.

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“…Black pigmentation of both the aortic valve and the coronary arteries is a rare condition, and is described only sporadically [1]. There are two possible causes reported.…”

Section: Introductionmentioning

confidence: 99%

“…This enzymatic deficiency produces homogentisic acid (HGA) which accumulates in connective tissue, resulting in a blue-black pigmentation and degeneration of the affected tissue [2]. The diagnosis is based on a triad of homogentisic aciduria, ochronosis, and degenerative joint and spine arthropathy [1][2][3]. The cardiovascular presentation is rare, and it mainly involves the aortic valve, characterised by pigmentation and stenosis [1].…”

Section: Introductionmentioning

confidence: 99%

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Black aortic valve and coronary arteries in liver transplantation patient: case report

et al. 2023

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Background Black pigmentation of the aortic valve and coronary arteries has been reported to be caused by alkaptonuria or minocycline. In patients with liver transplantation it has been described only once, after exposure to minocycline. We report a second case of such pigmentation in a liver transplantation patient, for whom none of the known causes are an adequate explanation for this pigmentation. Case presentation Our 56-year-old male patient showed a complex history of two liver transplantations and sleeve gastrectomy, and had neither alkaptonuria nor a history of minocycline intake. He underwent an urgent coronary bypass grafting and aortic valve replacement because of an acute coronary syndrome based on three-vessel disease and progressive aortic valve stenosis. During this procedure, the aortic valve and coronary arteries had black pigmentation. Conclusions There are causes – other than alkaptonuria and minocycline – that can induce a black pigmentation of the aortic valve and coronary arteries. In patients with a history of liver transplantation, alteration in (dys)functional liver parenchyma or administration of substances related to the procedure of liver transplantation are possible causes. Identifying these is important because they are potentially harmful as they may induce degenerative changes and functional impairment of the aortic valve and coronary arteries. Further research is needed, but proves to be difficult due to the rare nature of this condition.

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A black heart: Aortic valve ochronosis secondary to alkaptonuria causing aortic stenosis

Cited by 4 publications

References 11 publications

Black Aortic Valve: Incidental Finding of Alkaptonuria

Black Aortic Valve: Incidental Finding of Alkaptonuria

Identification of Potential Inhibitors for the Treatment of Alkaptonuria Using an Integrated In Silico Computational Strategy

Black aortic valve and coronary arteries in liver transplantation patient: case report

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