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Bölsterli, B.K.* ; Boltshauser, E.* ; Palmieri, L.* ; Spenger, J.* ; Brunner-Krainz, M.* ; Distelmaier, F.* ; Freisinger, P.* ; Geis, T.* ; Gropman, A.L.* ; Häberle, J.* ; Hentschel, J.* ; Jeandidier, B.* ; Karall, D.* ; Keren, B.* ; Klabunde-Cherwon, A.* ; Konstantopoulou, V.* ; Kottke, R.* ; Lasorsa, F.M.* ; Makowski, C.* ; Mignot, C.* ; O'Gorman Tuura, R.* ; Porcelli, V.* ; Santer, R.* ; Sen, K.* ; Steinbrücker, K.* ; Syrbe, S.* ; Wagner, M. ; Ziegler, A.* ; Zöggeler, T.* ; Mayr, J.A.* ; Prokisch, H. ; Wortmann, S.B.*

Ketogenic diet treatment of defects in the mitochondrial malate aspartate shuttle and pyruvate carrier.

Nutrients 14:3605 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Agc1 ; Citrullinemia ; Aspartate Glutamate Carrier 1 Deficiency ; Citrin Deficiency ; Epilepsy ; Hepatopathy ; Mitochondrial Disease ; Modified Atkins Diet ; Serine ; Treatment
ISSN (print) / ISBN 2072-6643
e-ISSN 2072-6643
Zeitschrift Nutrients
Quellenangaben Band: 14, Heft: 17, Seiten: , Artikelnummer: 3605 Supplement: ,
Verlag MDPI
Verlagsort Basel
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Neurogenomics (ING)
Förderungen Swiss National Science Foundation
Elterninitiative Kinderkrebsklinik e.V.
Deutsche Forschungsgemeinschaft
FWF Austrian Science Fund
Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerlan