Bolsterli, Bigna K. and Boltshauser, Eugen and Palmieri, Luigi and Spenger, Johannes and Brunner-Krainz, Michaela and Distelmaier, Felix and Freisinger, Peter and Geis, Tobias and Gropman, Andrea L. and Haberle, Johannes and Hentschel, Julia and Jeandidier, Bruno and Karall, Daniela and Keren, Boris and Klabunde-Cherwon, Annick and Konstantopoulou, Vassiliki and Kottke, Raimund and Lasorsa, Francesco M. and Makowski, Christine and Mignot, Cyril and Tuura, Ruth O'Gorman and Porcelli, Vito and Santer, Rene and Sen, Kuntal and Steinbruecker, Katja and Syrbe, Steffen and Wagner, Matias and Ziegler, Andreas and Zoeggeler, Thomas and Mayr, Johannes A. and Prokisch, Holger and Wortmann, Saskia B. (2022) Ketogenic Diet Treatment of Defects in the Mitochondrial Malate Aspartate Shuttle and Pyruvate Carrier. NUTRIENTS, 14 (17): 3605. ISSN , 2072-6643
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | AGC1 DEFICIENCY; SLC25A13 GENE; MUTATIONS; CITRIN; MUSCLE; IDENTIFICATION; FREQUENCY; DIAGNOSIS; DISORDER; DISEASE; mitochondrial disease; epilepsy; hepatopathy; aspartate glutamate carrier 1 deficiency; AGC1; citrin deficiency; Citrullinemia; treatment; modified Atkins diet; serine |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Dec 2023 14:31 |
| Last Modified: | 12 Dec 2023 14:31 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58710 |
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