Black Heart at Surgery - Primary Diagnosis of Alkaptonuria at Surgery

Abstract

Alkaptonuria is a rare genetic disorder of tyrosine catabolism in which homogentisic acid accumulates leading to ochronotic deposition in connective tissue. This has widespread effects including degenerative arthritis and, more rarely, cardiovascular manifestations, the most common of which is aortic stenosis. We present a 66-year old patient in whom we diagnosed alkaptonuria during an aortic valve replacement for symptomatic aortic stenosis. We conducted a world literature review to examine the evidence for the prevalence of aortic valve disease and cardiac involvement in alkaptonuria. We discuss the pathogenesis of aortic valve ochronosis. Keywords:

Joint pain, black urine… and a heart murmur

“…Alkaptonuria was the first autosomal recessive congenital disorder described in humans [1]. Due to decreased homogentisate 1,2-dioxygenase activity, HGA (an intermediate metabolite in aromatic amino acid catabolic pathway) accumulates as a dark pigment [2]. This leads to the classic triad of black urine, dark pigmentation of some organs (named "ochronosis", frequently seen in sclera and helix cartilage) and joint degeneration.…”

“…However, these are not the only features of alkaptonuria: cardiovascular involvement is an important event that may occur. Although ochronosis has been described in different cardiovascular locations [1][2][3], aortic valve is the most commonly affected structure, and aortic stenosis appears in up to 19-25% of patients [2].…”

“…HGA may play an etiopathogenic role in valvulopathy development [3]. HGA has been postulated to accumulate in turbulent blood flow areas, acting as an irritating agent and triggering an inflammatory response, which leads to fibrosis and tissue calcification [2,3].…”

“…Symptomatic treatment of joint and cardiovascular complications is frequently needed, including valve replacement. There is controversy about which type of prosthetic valve (biological or mechanical) should be used [2]. Until more evidence is available, prosthesis choice is usually made accordingly to the recommendations for general population.…”