Special Issue "Inherited Metabolic Disease"

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Integrative Metabolomics".

Deadline for manuscript submissions: closed (30 November 2021).

Special Issue Editor

Dr. Maria Fuller
E-Mail
Guest Editor
1. Genetics and Molecular Pathology, SA Pathology (at Women's and Children's Hospital), Adelaide, Australia
2. Adelaide Medical School, University of Adelaide, Adelaide, Australia
Interests: lysosomal storage disorders; diagnosis of inborn errors of metabolism; understanding and treating inherited neurodegenerative disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Today more than 1000 inborn errors of metabolism (IEM) have been reported; arising from blocks in essential biochemical pathways that impair proper metabolism. Single gene disorders inherited as autosomal recessive traits predominate, although autosomal dominant and X-linked IEM are not uncommon. Metabolic defects in enzymes are the most frequently encountered but defects in transporters, ancillary proteins and co-factors also occur. The net result is a shortfall in energy production or accumulation of a toxic substrate. Clinical manifestations are diverse amongst both the spectrum of IEM and also within each individual disorder, and the majority impair neurological function. The prototype, phenylketonuiria, is acclaimed as neonates can be identified at birth by elevation of the metabolite, phenylalanine, from a heel-prick of blood allowing prompt dietary intervention sparing intellectual disability. However, for the majority of IEM much work awaits to allow early, accurate diagnosis and appropriate therapeutic intervention to significantly reduce morbidity, mortality and associated disabilities. This special issue is dedicated to the conglomerate of activity to achieve these goals, targeting reports of improvements in diagnosis, - including newborn and population screening - molecular mechanisms of diseases that advance our understanding of pathophysiology, and descriptions of current and novel, emerging therapies are also welcome.

Prof. Maria Fuller
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Inherited metabolic disease
  • Diagnosis, screening and treatment
  • Molecular mechanisms of genetic disease
  • Novel therapies for inherited metabolic disorders
  • Metabolomics
  • Laboratory diagnosis of inborn errors of metabolism
  • Cell and animal disease models

Published Papers (3 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Article
Differences of Phenylalanine Concentrations in Dried Blood Spots and in Plasma: Erythrocytes as a Neglected Component for This Observation
Metabolites 2021, 11(10), 680; https://doi.org/10.3390/metabo11100680 - 03 Oct 2021
Viewed by 518
Abstract
Monitoring phenylalanine (Phe) concentrations is critical for the management of phenylketonuria (PKU). This can be done in dried blood spots (DBS) or in EDTA plasma derived from capillary or venous blood. Different techniques are used to measure Phe, the most common being flow-injection [...] Read more.
Monitoring phenylalanine (Phe) concentrations is critical for the management of phenylketonuria (PKU). This can be done in dried blood spots (DBS) or in EDTA plasma derived from capillary or venous blood. Different techniques are used to measure Phe, the most common being flow-injection analysis tandem mass spectrometry (FIA-MS-MS) and ion exchange chromatography (IEC). Significant differences have been reported between Phe concentrations in various sample types measured by different techniques, the cause of which is not yet understood. We measured Phe concentrations in 240 venous blood samples from 199 patients with hyperphenylalaninemia in dried blood spots, EDTA plasma and erythrocytes by FIA-MS-MS and IEC. Phe concentrations were significantly lower in erythrocytes than in plasma leading to about 19% lower Phe DBS concentrations compared with plasma independent from the method used for quantification. As most therapy recommendations for PKU patients are based on plasma concentrations reliable conversion of DBS into plasma concentrations is necessary. Variances of Phe concentrations in plasma and DBS are not linear but increases with higher concentrations indicating heteroscedasticity. We therefore suggest the slope of the 75th percentile from quantile regression as a correction factor. Full article
(This article belongs to the Special Issue Inherited Metabolic Disease)
Show Figures

Figure 1

Article
Metabolic Outcomes of Anaplerotic Dodecanedioic Acid Supplementation in Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) Deficient Fibroblasts
Metabolites 2021, 11(8), 538; https://doi.org/10.3390/metabo11080538 - 13 Aug 2021
Viewed by 808
Abstract
Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD, OMIM 609575) is associated with energy deficiency and mitochondrial dysfunction and may lead to rhabdomyolysis and cardiomyopathy. Under physiological conditions, there is a fine balance between the utilization of different carbon nutrients to maintain the Krebs cycle. [...] Read more.
Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD, OMIM 609575) is associated with energy deficiency and mitochondrial dysfunction and may lead to rhabdomyolysis and cardiomyopathy. Under physiological conditions, there is a fine balance between the utilization of different carbon nutrients to maintain the Krebs cycle. The maintenance of steady pools of Krebs cycle intermediates is critical formitochondrial energy homeostasis especially in high-energy demanding organs such as muscle and heart. Even-chain dicarboxylic acids are established as alternative energy carbon sources that replenish the Krebs cycle by bypassing a defective β-oxidation pathway. Despite this, even-chain dicarboxylic acids are eliminated in the urine of VLCAD-affected individuals. In this study, we explore dodecanedioic acid (C12; DODA) supplementation and investigate its metabolic effect on Krebs cycle intermediates, glucose uptake, and acylcarnitine profiles in VLCAD-deficient fibroblasts. Our findings indicate that DODA supplementation replenishes the Krebs cycle by increasing the succinate pool, attenuates glycolytic flux, and reduces levels of toxic very long-chain acylcarnitines. Full article
(This article belongs to the Special Issue Inherited Metabolic Disease)
Show Figures

Figure 1

Article
Experience with the Urinary Tetrasaccharide Metabolite for Pompe Disease in the Diagnostic Laboratory
Metabolites 2021, 11(7), 446; https://doi.org/10.3390/metabo11070446 - 08 Jul 2021
Viewed by 977
Abstract
Following clinical indications, the laboratory diagnosis of the inherited metabolic myopathy, Pompe disease (PD), typically begins with demonstrating a reduction in acid alpha-glucosidase (GAA), the enzyme required for lysosomal glycogen degradation. Although simple in concept, a major challenge is defining reference intervals, as [...] Read more.
Following clinical indications, the laboratory diagnosis of the inherited metabolic myopathy, Pompe disease (PD), typically begins with demonstrating a reduction in acid alpha-glucosidase (GAA), the enzyme required for lysosomal glycogen degradation. Although simple in concept, a major challenge is defining reference intervals, as even carriers can have reduced GAA, and pseudodeficiencies complicate interpretation. Here, we developed a mass spectrometric assay for quantification of a urinary glycogen metabolite (tetrasaccharide) and reported on its utility as a confirmatory test for PD in a diagnostic laboratory. Using two age-related reference intervals, eight returned tetrasaccharide concentrations above the calculated reference interval but did not have PD, highlighting non-specificity. However, retrospective analysis revealed elevated tetrasaccharide in seven infantile-onset (IOPD) cases and sixteen late-onset (LOPD) cases, and normal concentrations in one heterozygote. Prospective tetrasaccharide analysis in nine individuals with reduced GAA confirmed IOPD in one, LOPD in six and identified two heterozygotes. Using this metabolite as a biomarker of therapeutic response was not overly informative; although most patients showed an initial drop following therapy initiation, tetrasaccharide concentrations fluctuated considerably and remained above reference intervals in all patients. While useful as a confirmation of PD, its utility as a biomarker for monitoring treatment warrants further investigation. Full article
(This article belongs to the Special Issue Inherited Metabolic Disease)
Show Figures

Figure 1

Back to TopTop