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A 64-year-old man, with history of hypertension and hypercholesterolemia, presented with chronic polyarthralgias and backache. He had brown-colored deposits in sclera and blueish pigmentation in helix of both ears (Fig. 1A, B). X-ray examination revealed prominent calcification of intervertebral discs (Fig. 1C). In addition, the patient reported episodes of black urine in his childhood. The color of a urine sample was initially normal, however, it turned blackish after several hours (Fig. 1D). 24-hour urine sample analysis showed high levels of homogentisic acid (HGA) (73,152 mg; normal range 0–10 mg).
Fig. 1(A) Scleral brown deposit (arrow). (B) Blueish pigmentation in helix. (C) Chest x-ray showing calcification of intervertebral discs. (D) Urine turned black after standing. (E) Black deposits (arrows) seen in aortic intima during surgery.(For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Cardiologic evaluation was requested since a grade IV/VI systolic heart murmur on aortic focus, radiating into the neck, was auscultated, consistent with aortic stenosis. Transthoracic echocardiography revealed severe aortic stenosis with mild left ventricular hypertrophy. When thoroughly asked, the patient also reported dyspnea and chest pain on exertion.
Finally, surgical aortic valve replacement was planned. During surgery, deposits of black pigment were seen both in aortic valve leaflets and aortic intima (Fig. 1E).
2. Diagnosis and discussion
Clinical findings raised the suspicion of alkaptonuria; elevated urinary levels of HGA confirmed this diagnosis.
Alkaptonuria was the first autosomal recessive congenital disorder described in humans [
]. Due to decreased homogentisate 1,2-dioxygenase activity, HGA (an intermediate metabolite in aromatic amino acid catabolic pathway) accumulates as a dark pigment [
]. 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 [
]. 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 [
]. 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 [
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