PuSH - Publication Server of Helmholtz Zentrum München: Ketogenic diet treatment of defects in the mitochondrial malate aspartate shuttle and pyruvate carrier.

Navigation

Home

Deutsch

Research

Advanced Search

Browse by ...

... Journal

... Publication Type

... Research Data

... Publication Year

Publication overview

Support & Contact

Contact persons

Help

Data protection

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)

Publ. Version/Full Text

Research data

DOI

PMC

	Open Access Gold

Abstract
Metrics
Extra information

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.

Altmetric

Additional Metrics?

[➜Log in]

Edit extra informations Login

Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords 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

Journal Nutrients

Quellenangaben Volume: 14, Issue: 17, Article Number: 3605

Publisher MDPI

Publishing Place Basel

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Neurogenomics (ING)

Grants 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