Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Mar 26;57(1):61-67.
doi: 10.2478/enr-2023-0008. Print 2023 Jan 1.

Nutritional interventions for patients with alkaptonuria: A minireview

Richard Imrich  1   2 , Andrea Zatkova  1 , Olga Lukacova  2 , Jana Sedlakova  2 , Elizabeth Zanova  2 , Miroslav Vlcek  1   2 , Adela Penesova  1   2 , Zofia Radikova  1   2 , Andrea Havranova  1   2 , Lakshminarayan Ranganath  3
Affiliations
Free article

Nutritional interventions for patients with alkaptonuria: A minireview

Richard Imrich et al. Endocr Regul. .
Free article

Abstract

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.

Keywords: alkaptonuria; nitisinone; nutritional intervention.

PubMed Disclaimer

References

    1. Bachmanov AA, Bosak NP, Glendinning JI, Inoue M, Li X, Manita S, McCaughey SA, Murata Y, Reed DR, Tordoff MG, Beauchamp GK. Genetics of amino acid taste and appetite. Adv Nutr 7, 806S–822S, 2016.
    1. Gallagher JA, Dillon JP, Sireau N, Timmis O, Ranganath LR. Alkaptonuria: An example of a “fundamental disease”-A rare disease with important lessons for more common disorders. Semin Cell Dev Biol 52, 53–57, 2016.
    1. Garrod AE. About Alkaptonuria. Med Chir Trans 85, 69–78, 1902.
    1. Granadino B, Beltran-Valero de Bernabe D, Fernandez-Canon JM, Penalva MA, Rodriguez de Cordoba S. The human homogentisate 1,2-dioxygenase (HGO) gene. Genomics 43, 115–122, 1997.
    1. Hughes JH, Wilson PJM, Sutherland H, Judd S, Hughes AT, Milan AM, Jarvis JC, Bou-Gharios G, Ranganath LR, Gallagher JA. Dietary restriction of tyrosine and phenylalanine lowers tyrosinemia associated with nitisi-none therapy of alkaptonuria. J Inherit Metab Dis 43, 259–268, 2020.

LinkOut - more resources