Ketogenic diets in patients with inherited metabolic disorders

Abstract

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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Abbreviations

ADSL:

Adenylosuccinate lyase

AEDs:

Antiepileptic drugs

ASL:

Argininosuccinate lyase

ATP:

Adenosine triphosphate

CoA:

Coenzyme A

CSF:

Cerebrospinal fluid

CKD:

Classical ketogenic diet

COX:

Cytochrome c oxidase

DNA:

Deoxyribonucleic acid

e.g:

For example

FADH2 :

Flavin adenine dinucleotide

GABA:

Gamma amino butyric acid

GLUT1-DS:

Glucose transporter type 1 deficiency syndrome

GSD/GSDs:

Glycogen storage disease/glycogen storage diseases

KD/KDs:

Ketogenic diet/ketogenic diets

IMD/IMDs:

Inherited metabolic disorder/inherited metabolic disorders

LGIT:

Low glycemic index treatment

MAD:

Modified Atkins diet

MCT:

Medium chain triglycerides

MELAS:

Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes

MtDNA:

Mitochondrial DNA

N:

Number

NADH + H+ :

Nicotinamide dinucleotide

NKH:

Non-ketotic hyperglycinemia

OXPHOS:

Oxidative phosphorylation

PDHc:

Pyruvate dehydrogenase complex

POLG:

Polymerase gamma

SSADH:

Succinic semialdehyde dehydrogenase

TCA:

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). https://doi.org/10.1007/s10545-015-9872-2

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Keywords

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