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The need for vigilance: false-negative screening for adenylosuccinate lyase deficiency caused by deribosylation of urinary biomarkers.
Clin Biochem 2013; 46(18):1899-901CB

Abstract

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.

Authors+Show Affiliations

Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Ke Karlovu 2, 128 08 Praha 2, Czech Republic. Electronic address: jkrijt@lf1.cuni.cz.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24183879

Citation

Krijt, Jakub, et al. "The Need for Vigilance: False-negative Screening for Adenylosuccinate Lyase Deficiency Caused By Deribosylation of Urinary Biomarkers." Clinical Biochemistry, vol. 46, no. 18, 2013, pp. 1899-901.
Krijt J, Skopova V, Adamkova V, et al. The need for vigilance: false-negative screening for adenylosuccinate lyase deficiency caused by deribosylation of urinary biomarkers. Clin Biochem. 2013;46(18):1899-901.
Krijt, J., Skopova, V., Adamkova, V., Cermakova, R., Jurecka, A., Kmoch, S., & Zikanova, M. (2013). The need for vigilance: false-negative screening for adenylosuccinate lyase deficiency caused by deribosylation of urinary biomarkers. Clinical Biochemistry, 46(18), pp. 1899-901. doi:10.1016/j.clinbiochem.2013.10.018.
Krijt J, et al. The Need for Vigilance: False-negative Screening for Adenylosuccinate Lyase Deficiency Caused By Deribosylation of Urinary Biomarkers. Clin Biochem. 2013;46(18):1899-901. PubMed PMID: 24183879.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The need for vigilance: false-negative screening for adenylosuccinate lyase deficiency caused by deribosylation of urinary biomarkers. AU - Krijt,Jakub, AU - Skopova,Vaclava, AU - Adamkova,Vaclava, AU - Cermakova,Renata, AU - Jurecka,Agnieszka, AU - Kmoch,Stanislav, AU - Zikanova,Marie, Y1 - 2013/10/30/ PY - 2013/07/26/received PY - 2013/10/04/revised PY - 2013/10/19/accepted PY - 2013/11/5/entrez PY - 2013/11/5/pubmed PY - 2014/8/27/medline KW - ADSL KW - Adenylosuccinate lyase deficiency KW - HPLC-DAD KW - LC–MS/MS KW - Purine metabolism KW - SA KW - SAICA KW - SAICA-riboside KW - SAdo KW - Succinyladenosine KW - Succinylaminoimidazole carboxamide riboside KW - Succinylpurines KW - TLC KW - adenylosuccinate lyase KW - adenylosuccinate lyase deficiency KW - dADSL KW - high-performance liquid chromatography with diode array detection KW - liquid chromatography–tandem mass spectrometry KW - succinyladenine KW - succinyladenosine KW - succinylaminoimidazole carboxamide KW - succinylaminoimidazole carboxamide riboside KW - thin-layer chromatography SP - 1899 EP - 901 JF - Clinical biochemistry JO - Clin. Biochem. VL - 46 IS - 18 N2 - 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. SN - 1873-2933 UR - https://www.unboundmedicine.com/medline/citation/24183879/The_need_for_vigilance:_false_negative_screening_for_adenylosuccinate_lyase_deficiency_caused_by_deribosylation_of_urinary_biomarkers_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0009-9120(13)00492-X DB - PRIME DP - Unbound Medicine ER -