Comparing the Phenylalanine/Tyrosine Pathway and Related Factors between Keratopathy and No-Keratopathy Groups as Well as between Genders in Alkaptonuria during Nitisinone Treatment



Ranganath, Lakshminarayan R, Milan, Anna M, Hughes, Andrew T, Davison, Andrew S ORCID: 0000-0001-5501-4475, Khedr, Milad, Imrich, Richard, Rudebeck, Mattias, Olsson, Birgitta, Norman, Brendan P ORCID: 0000-0001-9293-4852, Bou-Gharios, George
et al (show 1 more authors) (2022) Comparing the Phenylalanine/Tyrosine Pathway and Related Factors between Keratopathy and No-Keratopathy Groups as Well as between Genders in Alkaptonuria during Nitisinone Treatment. METABOLITES, 12 (8). 772-.

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Abstract

Nitisinone (NIT) causes tyrosinaemia and corneal keratopathy (KP), especially in men. However, the adaptation within the phenylalanine (PHE)/tyrosine (TYR) catabolic pathway during KP is not understood. The objective of this study is to assess potential differences in the PHE/TYR pathway during KP and the influence of gender in NIT-induced tyrosinaemia in alkaptonuria (AKU). Samples of serum and 24 h urine collected from patients treated with NIT during a 4-year randomized study in NIT vs. no-treatment controls (SONIA 2; Suitability Of Nitisinone In Alkaptonuria 2; EudraCT no. 2013-001633-41) at months 3 (V2), 12 (V3), 24 (V4), 36 (V5) and 48 (V6) were included in these analyses. Homogentisic acid (HGA), TYR, PHE, hydroxyphenylpyruvate (HPPA), hydroxyphenyllactate (HPLA) and sNIT were analysed at all time-points in serum and urine in the NIT-group. All statistical analyses were post hoc. Keratopathy occurred in 10 out of 69 AKU patients, eight of them male. Thirty-five sampling points (serum and 24 h urine) were analysed in patients experiencing KP and 272 in those with no-KP (NKP) during NIT therapy. The KP group had a lower HPLA/TYR ratio and a higher TYR/PHE ratio compared with the NKP group (<i>p</i> &lt; 0.05 for both). There were 24, 45, 100 and 207 sampling points (serum and 24 h urine) in the NIT group which were pre-NIT female, pre-NIT male, NIT female and NIT male, respectively. The PHE/TYR ratio and the HPLA/TYR ratio were lower in males (<i>p</i> &lt; 0.001 and <i>p</i> &lt; 0.01, respectively). In the KP group and in the male group during NIT therapy, adaptive responses to minimise TYR formation were impaired compared to NKP group and females, respectively.

Item Type: Article
Uncontrolled Keywords: sex, keratopathy, alkaptonuria, homogentisic acid, hydroxyphenylpyruvate, hydroxyphenyllactate, phenylalanine, tyrosinaemia
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 04 Nov 2022 10:56
Last Modified: 18 Jan 2023 19:48
DOI: 10.3390/metabo12080772
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3165988