Untargeted metabolomic analysis of urine samples in the diagnosis of some inherited metabolic disorders

Abstract

Background. Metabolomics is becoming an important tool in clinical research and the diagnosis of human diseases. It has been used in the diagnosis of inherited metabolic disorders with pronounced biochemical abnormalities. The aim of this study was to determine if it could be applied in the diagnosis of inherited metabolic disorders (IMDs) with less clear biochemical profiles from urine samples using an untargeted metabolomic approach. Methods. A total of 14 control urine samples and 21 samples from infants with cystinuria, maple syrup urine disease, adenylosuccinate lyase deficiency and galactosemia were tested. Samples were analyzed by liquid chromatography on aminopropyl column in aqueous normal phase separation system using gradient elution of acetonitrile/ammonium acetate. Detection was performed by time-of-flight mass spectrometer fitted with electrospray ionisation in positive mode. The data were statistically processed using principal component analysis (PCA), principal component discriminant function analysis (PCA-DFA) and partial least squares (PLS) regression. Results. All patient samples were first distinguished from controls using unsupervised PCA. Discrimination of the patient samples was then unambiguously verified using supervised PCA-DFA. Known markers of the diseases in question were successfully confirmed and a potential new marker emerged from the PLS regression. Conclusion. This study showed that untargeted metabolomics can be applied in the diagnosis of mild IMDs with less clear biochemical profiles.

Diagnosis of adenylosuccinate lyase deficiency by metabolomic profiling in plasma reveals a phenotypic spectrum

“…This highlights the utility of metabolomic profiling as a functional study in assessing the pathogenicity of variants of unknown significance. A similar untargeted metabolomics analysis using urine samples was reported last year whereas here, we show diagnosis of ADSL deficiency using plasma samples [25] . These cases of ADSL deficiency highlight the use of metabolomic profiling as a screening tool, as multiple common and rare metabolic disorders may be screened for in a single test rather than requiring multiple targeted and specific tests and allowing for the identification of individuals who may have less common presentations of disease [4] , [7] .…”

Metabolomic Profiling of Human Urine as a Screen for Multiple Inborn Errors of Metabolism

“…The analysis of the quantity of these biochemicals can provide evidence for perturbations in various physiological processes and thereby serve as biomarkers of disease. Profiling of urine samples for IEMs has been characterized previously using urine organic acid tests, but these methods utilized a single chromatographic separation (Kuhara, 2005), or a relatively limited biochemical library ( Janeckova et al, 2015).…”

Noninvasive Metabolic Profiling for Painless Diagnosis of Human Diseases and Disorders

“…Urinary metabolic profiling was also used for screening of 5-day-old newborns for neonatal galactosuria [35]. Nontargeted metabolic profiling by analysis of urine samples collected from infants has been successfully used in the diagnosis of some inborn metabolic disorders such as cystinuria, maple syrup urine disease, adenylosuccinate lyase deficiency and galactosemia [36]. In order to identify urinary biomarkers associated with nutritional rickets in children and to establish a noninvasive diagnosis method, urinary metabolic profiling along with metabolic pathway analysis was used to investigate the metabolic alterations associated with the disease [37].…”