Alkaptonuria: Current Perspectives

The Application of Clinical Genetics
Andrea ZatkovaLudevit Kadasi

Abstract

The last 15 years have been the most fruitful in the history of research on the metabolic disorder alkaptonuria (AKU). AKU is caused by a deficiency of homogentisate dioxygenase (HGD), the enzyme involved in metabolism of tyrosine, and is characterized by the presence of dark ochronotic pigment in the connective tissue that is formed, due to high levels of circulating homogentisic acid. Almost 120 years ago, Sir Archibald Garrod used AKU to illustrate the concept of Mendelian inheritance in man. In January 2019, the phase III clinical study SONIA 2 was completed, which tested the effectiveness and safety of nitisinone in the treatment of AKU. Results were positive, and they will serve as the basis for the application for registration of nitisinone for treatment of AKU at the European Medicines Agency. Therefore, AKU might become a rare disease for which a cure will be found by 2020. We understand the natural history of the disease and the process of ochronosis much more, but at the same time there are still unanswered questions. One of them is the issue of the factors influencing the varying severity of the disease, since our recent genotype-phenotype study did not show that differences in residual homogentisic acid activity ca...Continue Reading

Citations

Sep 11, 2021·European Journal of Human Genetics : EJHG·Andrea SoltysovaAndrea Zatkova

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Methods Mentioned

BETA
biopsy
gene trap
protein folding
Knockout
differential scanning calorimetry

Software Mentioned

SOFIA
Stability
PPI
mCSM
DevelopAKUre
Lig
SOFIA (

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