MSACL 2019 US Abstract

Nitisinone: Short and Long Term Effects on Tyrosine Metabolites in Alkaptonuria and Unmasking of the Ochronotic Pathway

Anna M Milan (1,2), Andrew T Hughes (1,2), Andrew S Davison (1,2), Milad Khedr (1), James A Gallagher (2), Lakshminarayan Ranganath (1,2)
(1) Department of Clinical Biochemistry and Metabolic Medicine, Liverpool Clinical Laboratories, Royal Liverpool & Broadgreen University Hospital Trust, Liverpool, UK (2) Institute of Ageing and Chronic Disease, Musculoskeletal Biology I, University of Liverpool, UK

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Anna Milan (Presenter) Royal Liverpool University Hospital

Presenter Bio: Anna Milan is a Consultant Clinical Scientist and Honorary Lecturer working within Liverpool Clinical Laboratories. Her interests lie in Alkpatonuria, bone markers, Vitamin D and connective tissue biochemistry. She has an extensive research background in mineralised tissue biochemistry prior to entering the NHS, where she continues to maintain a balance between clinical service provison and R&D. She has presented both nationionally and internationally and is part of the DevelopAKUre Consortium working towards an effective treatment for alkaptonuria.

Relevant Financial Disclosures (within past 24 months) No relevant financial relationship(s) to disclose. Discussing Products? NO, presenter will NOT present educational content related to products/services of the ineligible company(ies) listed above. Conflict mitigation NOT REQUIRED.

Nitisinone reduces urinary and circulating homogentisic acid in Alkaptonuria and therein alleviates the burden on the associated detrimental ochronotic pathway. We report the quantitation of tyrosine pathway organic acids hydroxyphenyllactic (HPLA) and hydroxyphenylpyruvic acid (HPPA), by LC-MS/MS in both short term, multi-dose nitisinone treatment (SONIA 1 study, multi-centre) and long-term 2mg daily dose (National AKU Centre, Liverpool UK). Data demonstrates significantly higher concentrations of tyrosine metabolites, post-nitisinone (p<0.01 at all doses) with a dose dependant but not time dependant effect. We postulate that blocking pigment formation unmasks the metabolite flux which leads to ochronotic pigment formation.