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.