DISCUSSION
Alkaptonuria occurs in 1/250,000–1/1,000,000 people.1In consanguineous groups, the incidence may be as high as 1/25,000.2 The enzyme deficiency prevents the breakdown of HGA to fumaric and acetoacetic acids, resulting in an increased concentration of HGA in the urine and many tissues. This causes the classic clinical triad of dark urine at birth, ochronosis, and degenerative ochronotic arthropathy. The effect of HGA accumulation on the cardiovascular system is usually discovered at 60–70 years of age. Alkaptonuria often remains undiagnosed in childhood because urine discoloration can only be detected in urine that has been left standing. Furthermore, because of the lack of specific symptoms, it is diagnosed postoperatively due to arthropathy or valvular disease.
No guidelines exist for optimal prosthetic valve selection for AVR. Because the bioprostheses may be exposed to ochronotic pigment-related valvular calcification like the native valve tissue, several case reports have recommended the use of mechanical prostheses.3,4,5 However, structural valve deterioration due to ochronosis in bioprostheses has not been described, and only one study reported on the functionality of the bioprosthetic valve after the patient was discharged.6 For this patient, we chose a bioprosthesis preoperatively considering her age and surgical risks and benefits. Follow-up echocardiography performed 3 years postoperatively revealed no evidence of structural valve deterioration. It may take time for the prosthetic valve to deteriorate because the ochronotic pigment must accumulate. Further studies involving more cases are needed to determine the optimal choice of prostheses in patients with alkaptonuria.
Although there is no standard treatment for alkaptonuria, the prognosis is relatively good. Currently, the treatment is only palliative.7 Nitisinone inhibits 4-hydroxyphenylpyruvate dioxygenase, the enzyme that causes HGA formation, dramatically reducing the production and urinary excretion of HGA.8 Taking 2 mg/day of nitisinone slows the clinical progression of alkaptonuria, decreases HGA levels, and arrests ochronosis, the cause of tissue damage in alkaptonuria.9 Therefore, nitisinone may be one of the safest treatments to prevent the progression of calcification in the native aortic or bioprosthetic valve. However, due to limited data on aortic valve disease, we did not use this drug in our patient. Further studies are needed to determine the safety and long-term efficacy of long-term nitisinone use when treating alkaptonuria.
In conclusion, alkaptonuria should be considered when tissue pigmentation and arthritis are present, along with valvular disease and coronary artery calcification. Routine echocardiography is recommended in patients older than 50 years diagnosed with alkaptonuria. The short-term outcomes were good, but data on the long-term outcomes that could help regulate the selection of prosthetic valves to treat AS are limited. Thus, further research is needed on the selection of a prosthesis in patients with alkaptonuria and to understand the natural history of AS and the rate of structural valve deterioration after bioprosthesis AVR.