Urea Cycle Related Amino Acids Measured in Dried Bloodspots Enable Long-Term In Vivo Monitoring and Therapeutic Adjustment

Julien Baruteau; Youssef Khalil; Stephanie Grunewald; Marta Zancolli; Anupam Chakrapani; Maureen Cleary; James Davison; Emma Footitt; Simon N Waddington; Paul Gissen; Philippa Mills

doi:10.3390/metabo9110275

Urea Cycle Related Amino Acids Measured in Dried Bloodspots Enable Long-Term In Vivo Monitoring and Therapeutic Adjustment

Metabolites. 2019 Nov 12;9(11):275. doi: 10.3390/metabo9110275.

Authors

Julien Baruteau^{1

2

3

4}, Youssef Khalil¹, Stephanie Grunewald³, Marta Zancolli⁴, Anupam Chakrapani³, Maureen Cleary³, James Davison³, Emma Footitt³, Simon N Waddington^{2

5}, Paul Gissen^{1

2

6}, Philippa Mills¹

Affiliations

¹ Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London WC1E 6BT, UK.
² Gene Transfer Technology Group, Institute for Women's Health, University College London, London WC1E 6BT, UK.
³ Metabolic Medicine Department, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK.
⁴ National Institute of Health Research Great Ormond Street Hospital Biomedical Research Centre, London W1T 7HA, UK.
⁵ Wits/SAMRC Antiviral Gene Therapy Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa.
⁶ MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK.

Abstract

Background: Dried bloodspots are easy to collect and to transport to assess various metabolites, such as amino acids. Dried bloodspots are routinely used for diagnosis and monitoring of some inherited metabolic diseases.

Methods: Measurement of amino acids from dried blood spots by liquid chromatography-tandem mass spectrometry.

Results: We describe a novel rapid method to measure underivatised urea cycle related amino acids. Application of this method enabled accurate monitoring of these amino acids to assess the efficacy of therapies in argininosuccinate lyase deficient mice and monitoring of these metabolites in patients with urea cycle defects.

Conclusion: Measuring urea cycle related amino acids in urea cycle defects from dried blood spots is a reliable tool in animal research and will be of benefit in the clinic, facilitating optimisation of protein-restricted diet and preventing amino acid deprivation.

Keywords: amino acids; argininosuccinate lyase; dried blood spots; tandem mass spectrometry; urea cycle.

Abstract

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