The need for vigilance: false-negative screening for adenylosuccinate lyase deficiency caused by deribosylation of urinary biomarkers
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
24183879
DOI
10.1016/j.clinbiochem.2013.10.018
PII: S0009-9120(13)00492-X
Knihovny.cz E-resources
- Keywords
- ADSL, Adenylosuccinate lyase deficiency, HPLC-DAD, LC–MS/MS, Purine metabolism, SA, SAICA, SAICA-riboside, SAdo, Succinyladenosine, Succinylaminoimidazole carboxamide riboside, Succinylpurines, TLC, adenylosuccinate lyase, adenylosuccinate lyase deficiency, dADSL, high-performance liquid chromatography with diode array detection, liquid chromatography–tandem mass spectrometry, succinyladenine, succinyladenosine, succinylaminoimidazole carboxamide, succinylaminoimidazole carboxamide riboside, thin-layer chromatography,
- MeSH
- Adenosine analogs & derivatives urine MeSH
- Adenylosuccinate Lyase deficiency urine MeSH
- Aminoimidazole Carboxamide analogs & derivatives metabolism urine MeSH
- Autistic Disorder MeSH
- Bacterial Proteins metabolism MeSH
- Chromatography, Thin Layer methods MeSH
- Enterococcus faecalis MeSH
- Enzymes metabolism MeSH
- False Negative Reactions MeSH
- Klebsiella pneumoniae MeSH
- Humans MeSH
- Urine microbiology MeSH
- Purine-Pyrimidine Metabolism, Inborn Errors diagnosis urine MeSH
- Child, Preschool MeSH
- Ribonucleosides metabolism urine MeSH
- Tandem Mass Spectrometry methods MeSH
- Chromatography, High Pressure Liquid MeSH
- Check Tag
- Humans MeSH
- Child, Preschool MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Adenosine MeSH
- Adenylosuccinate Lyase MeSH
- Aminoimidazole Carboxamide MeSH
- Bacterial Proteins MeSH
- Enzymes MeSH
- Ribonucleosides MeSH
- succinyladenosine MeSH Browser
- succinylaminoimidazole carboxamide riboside MeSH Browser
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 2.7mmol/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.
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