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Bölsterli, Bigna K. [Author]; Boltshauser, Eugen [Author]; Palmieri, Luigi [Author]; Spenger, Johannes [Author]; Brunner-Krainz, Michaela [Author]; Distelmaier, Felix [Author]; Freisinger, Peter [Author]; Geis, Tobias [Author]; Gropman, Andrea L. [Author]; Häberle, Johannes [Author]; Hentschel, Julia [Author]; Jeandidier, Bruno [Author]; Karall, Daniela [Author]; Keren, Boris [Author]; Klabunde-Cherwon, Annick [Author]; Konstantopoulou, Vassiliki [Author]; Kottke, Raimund [Author]; Lasorsa, Francesco M. [Author]; Makowski, Christine [Author]; Mignot, Cyril [Author]; O'Gorman Tuura, Ruth [Author]; Porcelli, Vito [Author]; Santer, René [Author]; Sen, Kuntal [Author]; [...]

Ketogenic Diet Treatment of Defects in the Mitochondrial Malate Aspartate Shuttle and Pyruvate Carrier

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  • Media type: E-Article
  • Title: Ketogenic Diet Treatment of Defects in the Mitochondrial Malate Aspartate Shuttle and Pyruvate Carrier
  • Contributor: Bölsterli, Bigna K. [Author]; Boltshauser, Eugen [Author]; Palmieri, Luigi [Author]; Spenger, Johannes [Author]; Brunner-Krainz, Michaela [Author]; Distelmaier, Felix [Author]; Freisinger, Peter [Author]; Geis, Tobias [Author]; Gropman, Andrea L. [Author]; Häberle, Johannes [Author]; Hentschel, Julia [Author]; Jeandidier, Bruno [Author]; Karall, Daniela [Author]; Keren, Boris [Author]; Klabunde-Cherwon, Annick [Author]; Konstantopoulou, Vassiliki [Author]; Kottke, Raimund [Author]; Lasorsa, Francesco M. [Author]; Makowski, Christine [Author]; Mignot, Cyril [Author]; O'Gorman Tuura, Ruth [Author]; Porcelli, Vito [Author]; Santer, René [Author]; Sen, Kuntal [Author]; [...]
  • Published: Basel: MDPI, [2023]
  • Published in: Nutrients ; 14, (2022)
  • Language: English
  • Keywords: modified Atkins diet ; AGC1 ; treatment ; serine ; Citrullinemia ; hepatopathy ; citrin deficiency ; epilepsy ; aspartate glutamate carrier 1 deficiency ; mitochondrial disease
  • Origination:
  • Footnote:
  • Description: Themitochondrialmalate aspartate shuttle system(MAS)maintains the cytosolicNAD+/NADHredox balance, thereby sustaining cytosolic redox-dependent pathways, such as glycolysis andserine biosynthesis. Human disease has been associated with defects in four MAS-proteins (encodedby MDH1, MDH2, GOT2, SLC25A12) sharing a neurological/epileptic phenotype, as wellas citrin deficiency (SLC25A13) with a complex hepatopathic-neuropsychiatric phenotype. Ketogenicdiets (KD) are high-fat/low-carbohydrate diets, which decrease glycolysis thus bypassing thementioned defects. The same holds for mitochondrial pyruvate carrier (MPC) 1 deficiency, whichalso presents neurological deficits. We here describe 40 (18 previously unreported) subjects withMAS-/MPC1-defects (32 neurological phenotypes, eight citrin deficiency), describe and discuss theirphenotypes 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 astriking effect against seizures. Two individuals with citrin deficiency deceased before the correctdiagnosis was established, presumably due to high-carbohydrate treatment. Six citrin-deficient individualsreceived a carbohydrate-restricted/fat-enriched diet and showed normalisation of laboratoryvalues/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 ofproper treatment and can even be lifesaving.
  • Access State: Open Access
  • Rights information: Attribution (CC BY)