Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Bolsterli, BK; Boltshauser, E; Palmieri, L; Spenger, J; Brunner-Krainz, M; Distelmaier, F; Freisinger, P; Geis, T; Gropman, AL; Haberle, J; Hentschel, J; Jeandidier, B; Karall, D; Keren, B; Klabunde-Cherwon, A; Konstantopoulou, V; Kottke, R; Lasorsa, FM; Makowski, C; Mignot, C; Tuura, RO; Porcelli, V; Santer, R; Sen, K; Steinbrucker, K; Syrbe, S; Wagner, M; Ziegler, A; Zoggeler, T; Mayr, JA; Prokisch, H; Wortmann, SB.
Ketogenic Diet Treatment of Defects in the Mitochondrial Malate Aspartate Shuttle and Pyruvate Carrier
NUTRIENTS. 2022; 14(17): 3605
Doi: 10.3390/nu14173605
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-authors Med Uni Graz
- Brunner-Krainz Michaela
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- 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.
- Find related publications in this database (Keywords)
- mitochondrial disease
- epilepsy
- hepatopathy
- aspartate glutamate carrier 1 deficiency
- AGC1
- citrin deficiency
- Citrullinemia
- treatment
- modified Atkins diet
- serine