Untargeted metabolomics as an unbiased approach to the diagnosis of inborn errors of metabolism of the non-oxidative branch of the pentose phosphate pathway.
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AuthorsShayota, Brian J
Donti, Taraka R
Kennedy, Adam D
Bjornsson, Hans T
Berry, Gerard T
Pappan, Kirk L
Sutton, V Reid
Elsea, Sarah H
MetadataShow full item record
CitationShayota BJ, Donti TR, Xiao J, Gijavanekar C, Kennedy AD, Hubert L, et al. Untargeted metabolomics as an unbiased approach to the diagnosis of inborn errors of metabolism of the non-oxidative branch of the pentose phosphate pathway. Molecular genetics and metabolism. 2020;131(1-2):147-54.doi:10.1016/j.ymgme.2020.07.013.
AbstractInborn errors of metabolism (IEM) involving the non-oxidative pentose phosphate pathway (PPP) include the two relatively rare conditions, transketolase deficiency and transaldolase deficiency, both of which can be difficult to diagnosis given their non-specific clinical presentations. Current biochemical testing approaches require an index of suspicion to consider targeted urine polyol testing. To determine whether a broad-spectrum biochemical test could accurately identify a specific metabolic pattern defining IEMs of the non-oxidative PPP, we employed the use of clinical metabolomic profiling as an unbiased novel approach to diagnosis. Subjects with molecularly confirmed IEMs of the PPP were included in this study. Targeted quantitative analysis of polyols in urine and plasma samples was accomplished with chromatography and mass spectrometry. Semi-quantitative unbiased metabolomic analysis of urine and plasma samples was achieved by assessing small molecules via liquid chromatography and high-resolution mass spectrometry. Results from untargeted and targeted analyses were then compared and analyzed for diagnostic acuity. Two siblings with transketolase (TKT) deficiency and three unrelated individuals with transaldolase (TALDO) deficiency were identified for inclusion in the study. For both IEMs, targeted polyol testing and untargeted metabolomic testing on urine and/or plasma samples identified typical perturbations of the respective disorder. Additionally, untargeted metabolomic testing revealed elevations in other PPP metabolites not typically measured with targeted polyol testing, including ribonate, ribose, and erythronate for TKT deficiency and ribonate, erythronate, and sedoheptulose 7-phosphate in TALDO deficiency. Non-PPP alternations were also noted involving tryptophan, purine, and pyrimidine metabolism for both TKT and TALDO deficient patients. Targeted polyol testing and untargeted metabolomic testing methods were both able to identify specific biochemical patterns indicative of TKT and TALDO deficiency in both plasma and urine samples. In addition, untargeted metabolomics was able to identify novel biomarkers, thereby expanding the current knowledge of both conditions and providing further insight into potential underlying pathophysiological mechanisms. Furthermore, untargeted metabolomic testing offers the advantage of having a single effective biochemical screening test for identification of rare IEMs, like TKT and TALDO deficiencies, that may otherwise go undiagnosed due to their generally non-specific clinical presentations. Keywords: Developmental delay; Inborn error of metabolism; Metabolome; Pentose phosphate
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RightsCopyright © 2020 Elsevier Inc. All rights reserved.
- Transaldolase deficiency in a two-year-old boy with cirrhosis.
- Authors: Wamelink MM, Struys EA, Salomons GS, Fowler D, Jakobs C, Clayton PT
- Issue date: 2008 Jun
- Clinical and molecular characteristics of two transaldolase-deficient patients.
- Authors: Tylki-Szymanska A, Wamelink MM, Stradomska TJ, Salomons GS, Taybert J, Dąbrowska-Leonik N, Rurarz M
- Issue date: 2014 Dec
- Transaldolase deficiency: liver cirrhosis associated with a new inborn error in the pentose phosphate pathway.
- Authors: Verhoeven NM, Huck JH, Roos B, Struys EA, Salomons GS, Douwes AC, van der Knaap MS, Jakobs C
- Issue date: 2001 May
- Next-generation metabolic screening: targeted and untargeted metabolomics for the diagnosis of inborn errors of metabolism in individual patients.
- Authors: Coene KLM, Kluijtmans LAJ, van der Heeft E, Engelke UFH, de Boer S, Hoegen B, Kwast HJT, van de Vorst M, Huigen MCDG, Keularts IMLW, Schreuder MF, van Karnebeek CDM, Wortmann SB, de Vries MC, Janssen MCH, Gilissen C, Engel J, Wevers RA
- Issue date: 2018 May
- [Transaldolase deficiency - clinical outcome, pathogenesis, diagnostic process].
- Authors: Lipiński P, Stradomska T, Tylki-Szymańska A
- Issue date: 2018