Journal of Inherited Metabolic Disease

, Volume 29, Issue 2–3, pp 332–340 | Cite as

Anaplerotic diet therapy in inherited metabolic disease: Therapeutic potential

  • Charles R. Roe
  • Fanny Mochel


Beginning with phenylketonuria, dietary therapy for inborn errors has focused primarily on the restriction of the precursor to an affected catabolic pathway in an attempt to limit the production of potential toxins. Anaplerotic therapy is based on the concept that there may exist an energy deficit in these diseases that might be improved by providing alternative substrate for both the citric acid cycle (CAC) and the electron transport chain for enhanced ATP production. This article focuses on this basic problem, as it may relate to most catabolic disorders, and provides our current experience involving inherited diseases of mitochondrial fat oxidation, glycogen storage, and pyruvate metabolism using the anaplerotic compound triheptanoin. The observations have led to a realization that ‘inter-organ’ signalling and ‘nutrient sensors’ such as adenylate monophosphate mediated-protein kinase (AMPK) and mTOR (mammalian target of rapamycin) appear to play a significant role in the intermediary metabolism of these diseases. Activated AMPK turns on catabolic pathways to augment ATP production while turning off synthetic pathways that consume ATP. Information is provided regarding the inter-organ requirements for more normal metabolic function during crisis and how anaplerotic therapy using triheptanoin, as a direct source of substrate to the CAC for energy production, appears to be a more successful approach to an improved quality of life for these patients.


Glycogen Storage Disease Citric Acid Cycle Pyruvate Carboxylase Glycogen Storage Disease Type Glutamine Metabolism 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© SSIEM and Springer 2006

Authors and Affiliations

  1. 1.Institute of Metabolic DiseaseBaylor University Medical CenterDallasUSA
  2. 2.Necker Enfant MaladesParisFrance

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