Evaluation of the serum metabolome of patients with alkaptonuria before and after two years of treatment with nitisinone using LC‐QTOF‐MS

Background The homogentisic acid‐lowering therapy nitisinone is being evaluated for the treatment of alkaptonuria (AKU) at the National Centre for AKU. Beyond hypertyrosinemia, the wider metabolic consequences of its use are largely unknown. The aim of this work was to evaluate the impact of nitisin...

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Published in:JIMD reports 2019-07, Vol.48 (1), p.67-74
Main Authors: Davison, Andrew S., Norman, Brendan P., Ross, Gordon A., Hughes, Andrew T., Khedr, Milad, Milan, Anna M., Gallagher, James A., Ranganath, Lakshminarayan R.
Format: Article
Language:English
Subjects:
Acids
alkaptonuria
Chromatography
Mass spectrometry
Metabolism
Metabolites
metabolomics
nitisinone
Patients
Quality control
Research Report
Research Reports
Retention
Scientific imaging
tyrosine
Water purification
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Summary:Background The homogentisic acid‐lowering therapy nitisinone is being evaluated for the treatment of alkaptonuria (AKU) at the National Centre for AKU. Beyond hypertyrosinemia, the wider metabolic consequences of its use are largely unknown. The aim of this work was to evaluate the impact of nitisinone on the serum metabolome of patients with AKU after 12 and 24 months of treatment. Methods Deproteinized serum from 25 patients with AKU (mean age[±SD] 51.1 ± 14.9 years, 12 male) was analyzed using the 1290 Infinity II liquid chromatography system coupled to a 6550 quadrupole time‐of‐flight mass spectrometry (Agilent, UK). Raw data were processed using a batch targeted feature extraction algorithm and an accurate mass retention time database containing 469 intermediary metabolites (MW 72‐785). Matched entities (±10 ppm theoretical accurate mass and ±0.3 minutes retention time window) were filtered based on their frequency and variability (
ISSN:2192-8312
2192-8304
2192-8312
DOI:10.1002/jmd2.12042