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Inborn Errors of Metabolism
Published in Praveen S. Goday, Cassandra L. S. Walia, Pediatric Nutrition for Dietitians, 2022
Surekha Pendyal, Areeg Hassan El-Gharbawy
Use of triheptanoin as an effective therapy was approved in 2019 for the treatment of long-chain FAOD. Triheptanoin is an odd medium-chain triglyceride (7-carbon length) which when oxidized produces two acetyl-CoA as well as a propionyl-CoA. Propionyl-CoA becomes a source of energy by providing intermediates for the CA cycle. Use of triheptanoin has shown improved exercise endurance and reduction in major clinical events secondary to hypoglycemia, cardiomyopathy, and rhabdomyolysis in children and adults with long-chain FAOD.
Pyruvate carboxylase deficiency
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
A small number of patients have been treated with triheptanoin in an approach to anaplerotic therapy [49, 50]. The treatment has been deemed unsuccessful with deaths at seven and eight months [50] and six months [49]. However, in one of these patients [49] hepatic failure was reversed following treatment, and there was transport of C5 ketone bodies access the blood-brain barrier and increased concentrations of glutamine and γ-aminobutyric acid (GABA) in the CSF.
Adult polyglucosan body disease: an acute presentation leading to unmasking of this rare disorder
Published in Hospital Practice, 2022
Jaspreet Johal, Ramiro Castro Apolo, Michael W. Johnson, Michael R. Persch, Adam Edwards, Preet Varade, Hussam Yacoub
Early diagnosis of APBD may be essential for the design and efficacy of future therapeutic trials. Repletion of the defective lysosomal acid maltase has been proposed as a treatment for GSD-II, or Pompe disease. Since GBE activity associated with APBD is characterized by a late-onset, a therapeutic time window during which treatment can be offered has been proposed [30]. Enhancement of glycogen branching activity and cessation of the accumulation of polyglucosan has been proposed as a potential treatment strategy. Inhibition of the glycogen synthase (GYS) activity, which would alter the GYS/GBE activity ratio and halt glycogen synthesis and polyglucosan buildup [31,32], is an alternative strategy. Guaiacol, an inhibitor of GYS, constitutes a promising candidate for future therapy as preliminary studies in animal models with APBD showed reduced accumulation of polyglucosans and GBE activity in cardiac, liver, and peripheral nerve tissues with no reported adverse effects [30]. Kakhlon and colleagues reported a similar outcome using rapamycin and starvation to promote decreased activity of GYS [32]. There is also limited evidence that anaplerotic dietary therapy with triheptanoin may slow disease progression. Limited functional improvement was observed in a small number of affected individuals in the early stages of the disease, whereas other studies report no benefit [33,34]. In a randomized, placebo-controlled trial, triheptanoin supplementation failed to prevent disease progression in 23 patients [4], similar to findings reported recently in two siblings diagnosed with APBD [34].
Current challenges in the pathophysiology, diagnosis, and treatment of paroxysmal movement disorders
Published in Expert Review of Neurotherapeutics, 2021
Cécile Delorme, Camille Giron, David Bendetowicz, Aurélie Méneret, Louise-Laure Mariani, Emmanuel Roze
Triheptanoin is an odd medium C7 chain triglyceride that is eventually metabolized into acetyl-CoA (like even ketone bodies) and propionyl-CoA (unlike even ketone bodies), two key entries of the tricarboxylic acid cycle (Figure 2) [169]. This production of propionyl-CoA is what makes triheptanoin interesting in brain energy deficits. Importantly, treatment with triheptanoin should necessarily be associated with a restriction of dietary carbohydrates, particularly those with a high glycemic index [170]. In a pilot open-label trial, six GLUT1-DS patients showed a dramatic reduction of PMD with triheptanoin [171]. This effect was sustained over a three-year period in five of them [170]. Another pilot study on four patients indicated that triheptanoin might also be an option in patients with PMD while on KD, or patients who failed to be compliant to KD [172]. However, the initial switching period was challenging in these patients. Alongside the dietary treatment of PMD in GLUT1-DS patients, symptomatic treatments are usually disappointing, although acetazolamide can be helpful, at least in some patients [173,174].
Triheptanoin Supplementation Does not Affect Nutritional Status: A Case Report of Two Siblings With Adult Polyglucosan Body Disease
Published in Journal of the American College of Nutrition, 2020
Ramona De Amicis, Alessandro Leone, Stefano Ravasenghi, Graziana Scigliuolo, Elena Mauro, Ettore Salsano, Alberto Battezzati, Simona Bertoli
Triheptanoin is an oil containing a medium chain triglyceride with 7 carbon atoms (8.3 kcal/g), namely C7 heptanoate (C7TG), which is found in minimal quantities in certain seeds and produced commercially through the chemical breakdown of long-chain saturated fatty acids (1). Upon ingestion, C7TG rapidly splits in the gut into glycerol and three heptanoate molecules; the glycerol converts to pyruvate, while the heptanoate diffuses throughout the blood stream and tissue cells, where acts directly as fuel or is further metabolized in the liver to C4-ketone bodies (3-hydroxybutyrate and acetoacetate) and C5-ketone bodies (3-hydroxypentanoate and 3-ketopentanoate) via b-oxidation, thus refilling the pool of metabolic intermediates in the citric acid cycle and producing alternative fuel for brain and muscle cells (1–3).