| Popis: |
Alkaptonuria (AKU, OMIM, No. 203500) is a rare, slow-progressing, irreversible, multisystemic disease resulting from a deficiency of the homogentisate 1,2-dioxygenase enzyme, which leads to the accumulation of homogentisic acid (HGA) and subsequent deposition as pigment in connective tissues called ochronosis. As a result, severe arthropathy of large joints and spondyloarthropathy with frequent fractures, ligament ruptures, and osteoporosis develops in AKU patients. Since 2020, the first-time treatment with nitisinone has become available in the European Union. Nitisinone significantly reduces HGA production and arrests ochronosis in AKU patients. However, blocking of the tyrosine metabolic pathway by the drug leads to tyrosine plasma and tissue concentrations increase. The nitisinone-induced hypertyrosinemia can lead to the development of corneal keratopathy, and once it develops, the treatment needs to be interrupted. A decrease in overall protein intake reduces the risk of the keratopathy during nitisinone-induced hypertyrosinemia in AKU patients. The low-protein diet is not only poorly tolerated by patients, but over longer periods, leads to a severe muscle loss and weight gain due to increased energy intake from carbohydrates and fats. Therefore, the development of novel nutritional approaches is required to prevent the adverse events due to nitisinone-induced hypertyrosinemia and the negative impact on skeletal muscle metabolism in AKU patients. |
