Dokumentenart: | Artikel | ||||
---|---|---|---|---|---|
Höhe Gebühr (aus OpenAPC): | 2484.28 | ||||
Institution der Zahlung: | FWF - Austrian Science Fund | ||||
Titel eines Journals oder einer Zeitschrift: | Nutrients | ||||
Verlag: | MDPI | ||||
Ort der Veröffentlichung: | BASEL | ||||
Band: | 14 | ||||
Nummer des Zeitschriftenheftes oder des Kapitels: | 17 | ||||
Seitenbereich: | S. 3605 | ||||
Datum: | 2022 | ||||
Institutionen: | Medizin > Lehrstuhl für Kinder- und Jugendmedizin | ||||
Identifikationsnummer: |
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Stichwörter / 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 | ||||
Dewey-Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||
Status: | Veröffentlicht | ||||
Begutachtet: | Ja, diese Version wurde begutachtet | ||||
An der Universität Regensburg entstanden: | Ja | ||||
Dokumenten-ID: | 57737 |
Zusammenfassung
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) ...
Zusammenfassung
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.
Metadaten zuletzt geändert: 29 Feb 2024 13:02