Aortic stenosis and vascular calcifications in alkaptonuria

Abstract

Alkaptonuria is a rare metabolic disorder of tyrosine catabolism in which homogentisic acid (HGA) accumulates and is deposited throughout the spine, large joints, cardiovascular system, and various tissues throughout the body. In the cardiovascular system, pigment deposition has been described in the heart valves, endocardium, pericardium, aortic intima and coronary arteries. The prevalence of cardiovascular disease in patients with alkaptonuria varies in previous reports . We present a series of 76 consecutive adult patients with alkaptonuria who underwent transthoracic echocardiography between 2000 and 2009. A subgroup of 40 patients enrolled in a treatment study underwent non-contrast CT scans and these were assessed for vascular calcifications. Six of the 76 patients had aortic valve replacement. In the remaining 70 patients, 12 patients had aortic sclerosis and 7 patients had aortic stenosis. Unlike degenerative aortic valve disease, we found no correlation with standard cardiac risk factors. There was a modest association between the severity of aortic valve disease and joint involvement, however, we saw no correlation with urine HGA levels. Vascular calcifications were seen in the coronaries, cardiac valves, aortic root, descending aorta and iliac arteries. These findings suggest an important role for echocardiographic screening of alkaptonuria patients to detect valvular heart disease and cardiac CT to detect coronary artery calcifications.

Black Heart at Surgery - Primary Diagnosis of Alkaptonuria at Surgery

“…In the Cardiovascular Health Study, which looked at 5621 patients aged 65 or older, 1.8% were found to have aortic stenosis [7]. A series of 76 patients with alkaptonuria found aortic stenosis in 25% of patients over 65 [3]. Interestingly, unlike degenerative calcific aortic stenosis, the presence of stenosis was not correlated with the standard cardiovascular risk factors or age related calcification but was moderately correlated with the extent of joint involvement, another manifestation of alkaptonuria where homogenstisate is deposited in the connective tissue within cartilage.…”

“…The disease usually manifests late in life after the 4 th decade due to decline in renal clearance with age. Rarely, alkaptonuria can have cardiovascular manifestations: with ochronosis described in the heart valves, aorta, pericardium, endocardium and coronary arteries [3][4][5]. Aortic stenosis is the most commonly reported cardiovascular manifestation with a number of case series describing an increase in the prevalence of aortic stenosis compared to the general population.…”

Alkaptonuria-Associated Aortic Stenosis

“…The prevalence of aortic valve disease was reported significantly higher in patients with alkaptonuria. The two largest case studies to date include a series of 58 alkaptonuria patients, three (5.2%) of whom underwent aortic valve replacement, and a recent study by Hannoush et al of 76 alkaptonuria patients showing a 9% prevalence of aortic stenosis …”

“…Gaines and Pai suggested that the aortic valve dysfunction is caused by the degeneration of pigment‐laden fibrocytes, which may in turn stimulate progressive dystrophic calcification and fibrosis of leaflet tissue. Interestingly, there is no identifiable causal relationship between the conventional cardiovascular risk factors and the development of aortic valve disease …”

A patient survey on the impact of alkaptonuria symptoms as perceived by the patients and their experiences of receiving diagnosis and care

“…AKU is a multifaceted disease, with symptoms affecting individuals differently. Other features of AKU include arthritis, joint destruction, aortic stenosis, vascular calcifications, and dark urine due to the presence of HGA in the urine …”