The need for vigilance: false-negative screening for adenylosuccinate lyase deficiency caused by deribosylation of urinary biomarkers
| Autor: | Agnieszka Jurecka, Vaclava Skopova, Vaclava Adamkova, Marie Zikanova, Jakub Krijt, Renata Cermakova, Stanislav Kmoch |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Purine-Pyrimidine Metabolism Inborn Errors Adenosine Urinary system Clinical Biochemistry Urine Gastroenterology chemistry.chemical_compound Bacterial Proteins Liquid chromatography–mass spectrometry Tandem Mass Spectrometry Internal medicine medicine Enterococcus faecalis Humans Autistic Disorder Adenylosuccinate lyase Purine metabolism False Negative Reactions Chromatography High Pressure Liquid Adenylosuccinate lyase deficiency Creatinine Chromatography Metabolic disorder Adenylosuccinate Lyase General Medicine medicine.disease Aminoimidazole Carboxamide Enzymes Klebsiella pneumoniae chemistry Child Preschool Chromatography Thin Layer Ribonucleosides |
| Zdroj: | Clinical biochemistry. 46(18) |
| ISSN: | 1873-2933 |
| Popis: | Objectives Adenylosuccinate lyase deficiency (dADSL) is a rare inherited metabolic disorder. Biochemical diagnosis of the disease is based on the determination of enormously elevated urinary levels of succinylaminoimidazole carboxamide riboside (SAICA-riboside) and succinyladenosine (SAdo). We report a case of false negative screening for dADSL caused by deribosylation of the urinary biomarkers SAICA-riboside and SAdo. Design and methods A thin-layer chromatography (TLC) method with Pauly reagent detection of SAICA-riboside was used as a screening method. High-performance liquid chromatography with diode-array detection (HPLC-DAD) and LC–MS/MS methods were used for the identification and quantitative determination of SAICA-riboside, SAdo, succinylaminoimidazole carboxamide (SAICA) and succinyladenine (SA). Results Following a negative TLC screening in a known case of dADSL, we analyzed urine using HPLC-DAD. The concentration of SAICA-riboside was 2.7 mmol/mol creatinine (below the TLC detection limit), and we detected the two abnormal metabolites identified by LC–MS/MS as SAICA and SA. We showed that SAICA and SA were produced by deribosylation of SAICA-riboside and SAdo in the patient's urine. Studies performed by monitoring the production of SAICA and SA after the addition of SAICA-riboside and SAdo to the patient's urine and to urine samples from patients with urinary tract infections suggested that deribosylation is facilitated by bacterial enzymes. Conclusions Screening methods for the diagnosis of dADSL may be falsely negative due to bacteria-mediated deribosylation of SAICA-riboside and SAdo. HPLC-DAD or LC–MS/MS analyses allowing for simultaneous detection of SAICA-riboside, SAdo and their deribosylation products SAICA and SA should be preferentially used for the diagnosis of dADSL in urine. |
| Databáze: | OpenAIRE |
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