Multi‐omics in classical galactosemia: Evidence for the involvement of multiple metabolic pathways

Hermans, Merel E.; Weeghel, Michel van; Vaz, Frédéric M.; Ferdinandusse, Sacha; Hollak, Carla E. M.; Huidekoper, Hidde H.; Janssen, Mirian C. H.; Kuilenburg, André B. P.; Pras‐Raves, Mia L.; Wamelink, Mirjam M. C.; Wanders, Ronald J. A.; Welsink‐Karssies, Mendy M.; Bosch, Annet M.

doi:10.1002/jimd.12548

Cited by 11 publications

(10 citation statements)

References 25 publications

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“…Despite the emerging field of metabolomics as the newest Omics platform that focuses on metabolites, small molecules (<1,500 Da) hold promise to shine a light on the molecular mechanisms of several diseases, which may help for diagnostic and therapeutic purposes ( Jacob et al, 2019 ), very few studies have focused on GAL in humans biological fluids ( Janeckova et al, 2015 ; Taylor Fischer et al, 2019 ; Hermans et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

“…The pathophysiology of the long-term complication in GAL needs to be better understood, and predictive biomarkers need to be included ( Hermans et al, 2022 ). Prognostic uncertainty may lead to unnecessary or harmful treatment for patients with GAL, which burden patients and parents ( Knerr et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

“…Metabolomics has emerged as a potentially useful diagnostic and prognostic tool that might explain disease pathogenesis ( Masood et al, 2021 ; Jacob et al, 2022 ; Jans et al, 2022 ). There currently needs to be more investigations on the pathophysiology of GAL that concentrate on urine or blood metabolomics profiling ( Taylor Fischer et al, 2019 ; Hermans et al, 2022 ). Therefore, investigating the GAL metabolomics profile may aid in finding potential biomarkers, shed light on the mechanisms behind the disease’s progression, and ultimately aid in its early detection.…”

Section: Introductionmentioning

confidence: 99%

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Biomarker discovery in galactosemia: Metabolomics with UPLC/HRMS in dried blood spots

Alodaib

Nimer

Alhumaidy

et al. 2023

Front. Mol. Biosci.

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Introduction:Galactosemia (GAL) is a genetic disorder that results in disturbances in galactose metabolism and can lead to life-threatening complications. However, the underlying pathophysiology of long-term complications in GAL remains poorly understood.Methods: In this study, a metabolomics approach using ultra-performance liquid chromatography coupled with high-resolution mass spectrometry was used to investigate metabolomic changes in dried blood spots of 15 patients with GAL and 39 healthy individuals.Results: The study found that 2,819 metabolites underwent significant changes in patients with GAL compared to the control group. 480 human endogenous metabolites were identified, of which 209 and 271 were upregulated and downregulated, respectively. PA (8:0/LTE4) and ganglioside GT1c (d18:0/20:0) metabolites showed the most significant difference between GAL and the healthy group, with an area under the curve of 1 and 0.995, respectively. Additionally, the study identified potential biomarkers for GAL, such as 17-alpha-estradiol-3-glucuronide and 16-alpha-hydroxy DHEA 3-sulfatediphosphate.Conclusion: This metabolomics study deepened the understanding of the pathophysiology of GAL and presented potential biomarkers that might serve as prognostic biomarkers to monitor the progression or support the clinical diagnosis of GAL.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Biomarker discovery in galactosemia: Metabolomics with UPLC/HRMS in dried blood spots

Alodaib

Nimer

Alhumaidy

et al. 2023

Front. Mol. Biosci.

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“…Though RBCs are capable of transporting many carbohydrates across their membrane [109,110], they best utilize glucose to fuel energy metabolism with approximately 90% of glucose directed to glycolysis and the remaining 10% directed to the pentose phosphate pathway under normal, non-stress conditions [31,111]. Previous metabolomic experiments have revealed the ability of RBCs to metabolize citrate and other tricarboxylic acids [45] in addition to carbohydrates such as fructose, mannose [112], and galactose [113]. Though not immediately visible in healthy individuals, RBCs from individuals with different forms of glycogen storage disease have revealed residual activity of synthesis and degradation enzymes [114].…”

Section: Pathological Metabolic States Elucidate Metabolic Pathwaysmentioning

confidence: 99%

RBC-GEM: a Knowledge Base for Systems Biology of Human Red Blood Cell Metabolism

Haiman,

D’Alessandro,

Palsson

2024

Preprint

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Advancements with cost-effective, high-throughput omics technologies have had a transformative effect on both fundamental and translational research in the medical sciences. These advancements have facilitated a departure from the traditional view of human red blood cells (RBCs) as mere carriers of hemoglobin, devoid of significant biological complexity. Over the past decade, proteomic analyses have identified a growing number of different proteins present within RBCs, enabling systems biology analysis of their physiological functions. Here, we introduce RBC-GEM, the most extensive and meticulously curated metabolic reconstruction of a specific human cell type to-date. It was developed through meta-analysis of proteomic data from 28 studies published over the past two decades resulting in a RBC proteome composed of more than 4,600 distinct proteins. Through workflow-guided manual curation, we have compiled the metabolic reactions carried out by this proteome. RBC-GEM is hosted on a version-controlled GitHub repository, ensuring adherence to the standardized protocols for metabolic reconstruction quality control and data stewardship principles. This reconstruction of the RBC metabolic network is a knowledge base consisting of 718 genes encoding proteins acting on 1,590 unique metabolites through 2,554 biochemical reactions: a 700% size expansion over its predecessor. This reconstruction as an up-to-date curated knowledge base can be used for contextualization of data and for the construction of a computational whole-cell model of a human RBC.

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“…Classic galactosaemia (MIM 230400) is an inborn error of the metabolism caused by a deficiency in the enzyme galactose-1-phosphate uridyl transferase, which leads to the accumulation of galactose metabolites and causes severe liver disease, sepsis, and cataracts in infants, and long-term complications such as cognitive and ovarian dysfunction [ 1 ]. Its incidence is 1:19,000 to 1:44,000 in Europe and the United States, and it is more common in Ireland [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Lactose and Galactose Content in Spanish Cheeses: Usefulness in the Dietary Treatment of Patients with Galactosaemia

Vitoria

Melendreras²,

Vázquez-Palazón³

et al. 2023

Nutrients

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In galactosaemia, a strict galactose-free diet is necessary to prevent or resolve acute symptoms in infants. However, because the body produces up to 10 times more galactose than is found in a galactose-restricted diet, excessively restrictive diets should be avoided in children and adults to prevent nutritional deficiencies. Since cheese is a nutritional source of the calcium necessary for bone health, the latest international guidelines on the management of classical galactosaemia (2017) allow the consumption of cured cheeses with less than 25 mg of galactose/100 g and recommend that each country verifies the adequacy of the cheeses, since most mature cheeses do not always have a lower galactose content. In total, 32 cheese samples were purchased (19 Spanish and 13 international cheeses), and their lactose and galactose contents were analysed using ion chromatography with pulsed amperometric detection (IC-PAD). Five Spanish cheeses contained less than 25 mg of galactose/100 g: García Baquero semi-cured cheese; Hacendado, Gran Reserva and Mahón cured cheeses; and García Baquero Reserva 12-month cured cheese. In addition, eight international cheeses were confirmed as suitable: Comté, Gouda, Gruyere, Maasdam, Parmigiano, Edam, Emmental, and some samples of Cheddar. In addition to the well-known low-galactose Swiss and Dutch cheeses, according to the current results, five Spanish cheeses can be safely consumed. The greater availability of types of cheese favours better bone health in patients with galactosaemia.

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Multi‐omics in classical galactosemia: Evidence for the involvement of multiple metabolic pathways

Cited by 11 publications

References 25 publications

Biomarker discovery in galactosemia: Metabolomics with UPLC/HRMS in dried blood spots

Biomarker discovery in galactosemia: Metabolomics with UPLC/HRMS in dried blood spots

RBC-GEM: a Knowledge Base for Systems Biology of Human Red Blood Cell Metabolism

Lactose and Galactose Content in Spanish Cheeses: Usefulness in the Dietary Treatment of Patients with Galactosaemia

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