Urinary 2,8-dihydroxyadenine excretion in patients with adenine phosphoribosyltransferase deficiency, carriers and healthy control subjects.

Autor: Runolfsdottir HL; Internal Medicine Services, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland; Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland., Palsson R; Internal Medicine Services, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland; Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland; Division of Nephrology, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. Electronic address: runolfur@landspitali.is., Thorsteinsdottir UA; Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland, Reykjavik, Iceland., Indridason OS; Internal Medicine Services, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland; Division of Nephrology, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland., Agustsdottir IMS; Children's Medical Center, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland., Oddsdottir GS; Department of Clinical Biochemistry, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland., Thorsteinsdottir M; Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland, Reykjavik, Iceland; ArcticMass, Reykjavik, Iceland., Edvardsson VO; Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland; Children's Medical Center, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. Electronic address: vidare@landspitali.is.
Jazyk: angličtina
Zdroj: Molecular genetics and metabolism [Mol Genet Metab] 2019 Sep - Oct; Vol. 128 (1-2), pp. 144-150. Date of Electronic Publication: 2019 May 28.
DOI: 10.1016/j.ymgme.2019.05.015
Abstrakt: Background: Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder of adenine metabolism that results in excessive urinary excretion of the poorly soluble 2,8-dihydroxyadenine (DHA), leading to kidney stones and chronic kidney disease. The purpose of this study was to assess urinary DHA excretion in patients with APRT deficiency, heterozygotes and healthy controls, using a recently developed ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) assay.
Methods: Patients enrolled in the APRT Deficiency Registry and Biobank of the Rare Kidney Stone Consortium (http://www.rarekidneystones.org/) who had provided 24-h and first-morning void urine samples for DHA measurement were eligible for the study. Heterozygotes and healthy individuals served as controls. Wilcoxon-Mann-Whitney test was used to compare 24-h urinary DHA excretion between groups. Associations were examined using Spearman's correlation coefficient (r s ).
Results: The median (range) 24-h urinary DHA excretion was 138 (64-292) mg/24 h and the DHA-to-creatinine (DHA/Cr) ratio in the first-morning void samples was 13 (4-37) mg/mmol in APRT deficiency patients who were not receiving xanthine oxidoreductase inhibitor therapy. The 24-h DHA excretion was highly correlated with the DHA/Cr ratio in first-morning void urine samples (r s  = 0.84, p < .001). DHA was detected in all urine samples from untreated patients but not in any specimens from heterozygotes and healthy controls.
Conclusions: High urinary DHA excretion was observed in patients with APRT deficiency, while urine DHA was undetectable in heterozygotes and healthy controls. Our results suggest that the UPLC-MS/MS assay can be used for diagnosis of APRT deficiency.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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