Ketogenic diets in patients with inherited metabolic disorders


Ketogenic diets (KDs) are diets that bring on a metabolic condition comparable to fasting, usually without catabolism. Since the mid-1990s such diets have been widely used in patients with seizures/epilepsies, mostly children. This review focuses on the use of KDs in patients with various inherited metabolic disorders (IMD). In glucose transporter type 1 deficiency syndrome (GLUT1-DS) and pyruvate dehydrogenase complex (PDHc) deficiency, KDs are deemed the therapy of choice and directly target the underlying metabolic disorder. Moreover, in other IMD, mainly of intermediary metabolism such as glycogen storage diseases and disorders of mitochondrial energy supply, KDs may ameliorate clinical symptoms and laboratory parameters. KDs have also been used successfully to treat symptoms such as seizures/epilepsy in IMD, e.g. in urea cycle disorders and non-ketotic hyperglycinemia. As a note of caution, catabolism may cause the condition of patients with IMD to deteriorate and should thus be avoided during KDs. For this reason, careful monitoring (clinical, laboratory and apparatus-supported) is warranted. In some IMDs specific macronutrient supply is critical. Therefore, in cases of PDHc deficiency the carbohydrate intake tolerated without lactate increase and in urea cycle disorders the protein tolerance should be determined. Considering this, it is particularly important in patients with IMD that the use of KDs be individualized and well documented.

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Adenylosuccinate lyase


Antiepileptic drugs


Argininosuccinate lyase


Adenosine triphosphate


Coenzyme A


Cerebrospinal fluid


Classical ketogenic diet


Cytochrome c oxidase


Deoxyribonucleic acid


For example


Flavin adenine dinucleotide


Gamma amino butyric acid


Glucose transporter type 1 deficiency syndrome


Glycogen storage disease/glycogen storage diseases


Ketogenic diet/ketogenic diets


Inherited metabolic disorder/inherited metabolic disorders


Low glycemic index treatment


Modified Atkins diet


Medium chain triglycerides


Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes


Mitochondrial DNA



NADH + H+ :

Nicotinamide dinucleotide


Non-ketotic hyperglycinemia


Oxidative phosphorylation


Pyruvate dehydrogenase complex


Polymerase gamma


Succinic semialdehyde dehydrogenase


Tricarboxylic acid


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Correspondence to S. Scholl-Bürgi.

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Communicated by: Shamima Rahman

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Scholl-Bürgi, S., Höller, A., Pichler, K. et al. Ketogenic diets in patients with inherited metabolic disorders. J Inherit Metab Dis 38, 765–773 (2015).

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  • Ketogenic Diet
  • Glycogen Storage Disease
  • Urea Cycle Disorder
  • Inherit Metabolic Disorder
  • SSADH Deficiency