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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Ketogenic Diet Treatment of Defects in the Mitochondrial Malate Aspartate Shuttle and Pyruvate Carrier
Nutrients, Volume 14, No. 17, Article 3605, Year 2022
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Description
The mitochondrial malate aspartate shuttle system (MAS) maintains the cytosolic NAD+/NADH redox balance, thereby sustaining cytosolic redox-dependent pathways, such as glycolysis and serine biosynthesis. Human disease has been associated with defects in four MAS-proteins (encoded by MDH1, MDH2, GOT2, SLC25A12) sharing a neurological/epileptic phenotype, as well as citrin deficiency (SLC25A13) with a complex hepatopathic-neuropsychiatric phenotype. Ketogenic diets (KD) are high-fat/low-carbohydrate diets, which decrease glycolysis thus bypassing the mentioned defects. The same holds for mitochondrial pyruvate carrier (MPC) 1 deficiency, which also presents neurological deficits. We here describe 40 (18 previously unreported) subjects with MAS-/MPC1-defects (32 neurological phenotypes, eight citrin deficiency), describe and discuss their phenotypes and genotypes (presenting 12 novel variants), and the efficacy of KD. Of 13 MAS/MPC1-individuals with a neurological phenotype treated with KD, 11 experienced benefits—mainly a striking effect against seizures. Two individuals with citrin deficiency deceased before the correct diagnosis was established, presumably due to high-carbohydrate treatment. Six citrin-deficient individuals received a carbohydrate-restricted/fat-enriched diet and showed normalisation of laboratory values/hepatopathy as well as age-adequate thriving. We conclude that patients with MAS-/MPC1-defects are amenable to dietary intervention and that early (genetic) diagnosis is key for initiation of proper treatment and can even be lifesaving. © 2022 by the authors.
Authors & Co-Authors
Boltshauser, Eugen J.
Switzerland, Zurich
Kinderspital Zürich
Spenger, Johannes
Austria, Salzburg
Paracelsus Medizinische Privatuniversitat
Brunner-Krainz, Michaela
Austria, Graz
Medizinische Universität Graz
Distelmaier, Felix
Germany, Dusseldorf
Heinrich-heine-universität Düsseldorf
Freisinger, Peter
Germany, Reutlingen
Klinikum Reutlingen
Geis, Tobias
Germany, Regensburg
Universität Regensburg
Gropman, Andrea L.
United States, Washington, D.c.
Childrens National Health System
Häberle, Johannes
Switzerland, Zurich
Kinderspital Zürich
Switzerland, Zurich
Universität Zürich
Hentschel, Julia
Germany, Leipzig
Universität Leipzig
Karall, Daniela
Austria, Innsbruck
Medizinische Universitat Innsbruck
Keren, Boris
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Konstantopoulou, Vassiliki
Austria, Vienna
Medizinische Universität Wien
Kottke, Raimund
Switzerland, Zurich
Kinderspital Zürich
Lasorsa, Francesco Massimo
Italy, Bari
Università Degli Studi Di Bari Aldo Moro
Italy, Rome
Consiglio Nazionale Delle Ricerche
Makowski, Christine C.
Germany, Munich
Technische Universität München
Mignot, Cyril
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Santer, René
Germany, Hamburg
Universitätsklinikum Hamburg-eppendorf
Syrbe, Steffen
Germany, Heidelberg
Universitätsklinikum Heidelberg
Wagner, Matias
Germany, Munich
Technische Universität München
Germany, Munich
Ludwig-maximilians-universität München
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Ziegler, Andreas E.
Germany, Heidelberg
Universitätsklinikum Heidelberg
Mayr, Johannes Adalbert
Austria, Salzburg
Paracelsus Medizinische Privatuniversitat
Prokisch, Holger
Germany, Munich
Technische Universität München
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Wortmann, Saskia Brigitte
Austria, Salzburg
Paracelsus Medizinische Privatuniversitat
Netherlands, Nijmegen
Radboud University Medical Center
Statistics
Citations: 9
Authors: 23
Affiliations: 21
Identifiers
Doi:
10.3390/nu14173605
ISSN:
20726643
Research Areas
Genetics And Genomics
Study Design
Randomised Control Trial