Editing Alkaptonuria (section)

==Treatment==
In 2012 the  AKU Society formed a consortium called  DevelopAKUre to prove that [[nitisinone]], a drug already approved for treating another rare disease,  hereditary tyrosinaemia type-1, could be repurposed to treat AKU.{{cn|date=October 2024}}

The DevelopAKUre trials concluded in 2019 and successfully illustrated that nitisinone lowered levels of [[Homogentisic acid|homogentisic acid (HGA)]], the acid that causes the damage in AKU, by 99% which effectively halts the progression of the disease. In 2020, the [[European Medicines Agency]] and the [[European Commission]] approved the use of nitisinone for treating AKU making the treatment available to patients across the Europe and the UK.{{cn|date=October 2024}}

Nitisinone has revolutionised the treatment of AKU, however it can lead to a condition known as hypertyrosinaemia<ref>{{cite web | url=https://pubmed.ncbi.nlm.nih.gov/35201733 | pmid=35201733 | year=2023 | last1=Adnan | first1=M. | last2=Puranik | first2=S. | title=Hypertyrosinemia | publisher=StatPearls }}</ref> caused by elevated levels of the amino acid [[tyrosine]]. Hypertyrosinaemia can lead to serious symptoms including corneal keratopathy,<ref>{{cite journal | pmc=6122027 | year=2017 | last1=White | first1=A. | last2=c. Tchan | first2=M. | title=Nitisinone-Induced Keratopathy in Alkaptonuria: A Challenging Diagnosis Despite Clinical Suspicion | journal=Jimd Reports | volume=40 | pages=7–9 | doi=10.1007/8904_2017_56 | pmid=28879639 | isbn=978-3-662-57879-7 }}</ref> dermal toxicity,<ref>{{cite journal | pmc=4241204 | year=2014 | last1=Stewart | first1=R. M. | last2=Briggs | first2=M. C. | last3=Jarvis | first3=J. C. | last4=Gallagher | first4=J. A. | last5=Ranganath | first5=L. | title=Reversible Keratopathy Due to Hypertyrosinaemia Following Intermittent Low-Dose Nitisinone in Alkaptonuria: A Case Report | journal=Jimd Reports | volume=17 | pages=1–6 | doi=10.1007/8904_2014_307 | pmid=24997710 | isbn=978-3-662-44577-8 }}</ref>  neurodevelopment delay issues in children,<ref>{{cite journal | pmc=6488549 | year=2019 | last1=Davison | first1=A. S. | last2=Strittmatter | first2=N. | last3=Sutherland | first3=H. | last4=Hughes | first4=A. T. | last5=Hughes | first5=J. | last6=Bou-Gharios | first6=G. | last7=Milan | first7=A. M. | last8=Goodwin | first8=R. J. | last9=Ranganath | first9=L. R. | last10=Gallagher | first10=J. A. | title=Assessing the effect of nitisinone induced hypertyrosinaemia on monoamine neurotransmitters in brain tissue from a murine model of alkaptonuria using mass spectrometry imaging | journal=Metabolomics | volume=15 | issue=5 | page=68 | doi=10.1007/s11306-019-1531-4 | pmid=31037385 }}</ref> and alterations of wider metabolism.<ref>{{cite journal | pmc=9170613 | year=2021 | last1=Norman | first1=B. P. | last2=Davison | first2=A. S. | last3=Hughes | first3=J. H. | last4=Sutherland | first4=H. | last5=Wilson | first5=P. J. | last6=Berry | first6=N. G. | last7=Hughes | first7=A. T. | last8=Milan | first8=A. M. | last9=Jarvis | first9=J. C. | last10=Roberts | first10=N. B. | last11=Ranganath | first11=L. R. | last12=Bou-Gharios | first12=G. | last13=Gallagher | first13=J. A. | title=Metabolomic studies in the inborn error of metabolism alkaptonuria reveal new biotransformations in tyrosine metabolism | journal=Genes & Diseases | volume=9 | issue=4 | pages=1129–1142 | doi=10.1016/j.gendis.2021.02.007 | pmid=35685462 }}</ref> There is currently no effective treatment for hypertyrosinaemia other than limiting protein intake. Due to the potential side-effects of nitisinone treatment it is currently only prescribed to children aged 16 and above in Europe and patients will then have to follow a protein restricted diet and closely manage their tyrosine levels through frequent monitoring.{{cn|date=October 2024}}