Analyses of SLC13A5 -epilepsy patients reveal perturbations of TCA cycle

Abstract

Our results indicate that analysis of plasma citrate and other TCA analytes in SLC13A5 deficient patients define a diagnostic metabolic signature that can aid in diagnosing children with this disease.

Metabolomics to Improve the Diagnostic Efficiency of Inborn Errors of Metabolism

“…In practice, the subsequent reuse of metabolomic data collected for primary diagnostic purposes has already yielded benefits. Urine, plasma and CSF metabolomic assays have been employed, revealing significant findings on clinically analysed samples [58,[85][86][87][88]. These insights include new diagnostic biomarkers [87][88][89], a broader range of phenotype in adenylosuccinate lyase deficiency [90], insights around pre-analytical factors [91], primary metabolic variations from drug-related changes [92][93][94] and a better understanding of the underlying pathobiological mechanism of disease [95][96][97].…”

Improving liquid chromatography-tandem mass spectrometry determination of polycarboxylic acids in human urine by chemical derivatization. Comparison of o-benzyl hydroxylamine and 2-picolyl amine

“…Moreover, urine has been chosen as matrix model for method development. The suitability of urine in testing different approaches for TCA determination lies not only in its high relevance as a marker of several imbalances [26][27][28][29][30][31][32] but also in the great complexity of the matrix, the potential bacterial degradation of the samples and the high abundance of carboxylic acids which would hamper the proper derivatization of the analytes.…”

Metabolomics in the clinic: A review of the shared and unique features of untargeted metabolomics for clinical research and clinical testing

“…Clinical metabolomics testing, such as for IEM screening, is a nascent testing approach that is amenable to multiple sample types, can substitute tens of smaller assays, and represents an important proof‐of‐principle to support future pre‐clinical and clinical applications for metabolomics . Expanding on this, additional studies will provide new insights into acute and chronic diseases such as cardiovascular disease, hypertension, cancer, inflammatory disease, autoimmune disease, metabolic disorders, and neurological diseases.…”

“…With the end use clearly stated, it is recommended that the 100 s of metabolites from clinical metabolomics research be filtered to a short list of 1 to 10 biomarkers for subsequent targeted analytical assay development, validation, and algorithm development described by Xia et al 13 Clinical metabolomics testing, such as for IEM screening, is a nascent testing approach that is amenable to multiple sample types, [37][38][39] can substitute tens of smaller assays, and represents an important proof-of-principle to support future pre-clinical and clinical applications for metabolomics. [37][38][39]80,84,85,88,89,95,96 Expanding on this, additional studies will provide new insights into acute and chronic diseases such as cardiovascular disease, hypertension, cancer, inflammatory disease, autoimmune disease, metabolic disorders, and neurological diseases. Genome-wide association studies can link genotypes to biochemical profiles, 97,98 and future analyses will provide increased resolution into the penetrance of the genotypes and the clinical accuracy of the biochemical profiles associated with these genetic predispositions.…”

“…In addition to combining metabolomic and genomic data, a larger trend is to seamlessly integrate all patient information, such as test results from traditional clinical biochemistry (eg, enzymatic assays, protein assays), clinical ‘omics, and microbiome profiling. The combination of clinical metabolomics testing results, clinical biochemistry, and other ‘omics data streams has been shown to offer superior diagnostic power, in both IEM and wellness screenings, relative to the individual methods performed in isolation.…”