Tutorial: Triheptanoin and Nutrition Management for Treatment of Long-Chain Fatty Acid Oxidation Disorders.
anaplerotic
carnitine-acylcarnitine translocase deficiency
fatty acid oxidation disorder
medical nutrition therapy
triheptanoin
very long-chain acyl-CoA dehydrogenase deficiency
Journal
JPEN. Journal of parenteral and enteral nutrition
ISSN: 1941-2444
Titre abrégé: JPEN J Parenter Enteral Nutr
Pays: United States
ID NLM: 7804134
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
09
07
2020
revised:
22
09
2020
accepted:
14
10
2020
pubmed:
22
10
2020
medline:
22
4
2021
entrez:
21
10
2020
Statut:
ppublish
Résumé
Patients with severe long-chain fatty acid oxidation disorders (LC-FAODs) experience serious morbidity and mortality despite traditional dietary management including medium-chain triglyceride (MCT)-supplemented, low-fat diets. Triheptanoin is a triglyceride oil that is broken down to acetyl-coenzyme A (CoA) and propionyl-CoA, which replenishes deficient tricarboxylic acid cycle intermediates. We report the complex medical and nutrition management of triheptanoin therapy initiated emergently for 3 patients with LC-FAOD. Triheptanoin (Ultragenyx Pharmaceutical, Inc, Novato, CA, USA) was administered to 3 patients with LC-FAOD on a compassionate-use basis. Triheptanoin was mixed with non-MCT-containing low-fat formula. Patients were closely followed with regular cardiac and laboratory monitoring. Cardiac ejection fraction normalized after triheptanoin initiation. Patients experienced fewer hospitalizations related to metabolic crises while on triheptanoin. Patient 1 has tolerated oral administration without difficulty since birth. Patients 2 and 3 experienced increased diarrhea. Recurrent breakdown of the silicone gastrostomy tube occurred in patient 3, whereas the polyurethane nasogastric tube for patient 2 remained intact. Patient 3 experiences recurrent episodes of elevated creatine kinase levels and muscle weakness associated with illness. Patient 3 had chronically elevated C10-acylcarnitines while on MCT supplementation, which normalized after initiation of triheptanoin and discontinuation of MCT oil. Triheptanoin can ameliorate acute cardiomyopathy and increase survival in patients with severe LC-FAOD. Substituting triheptanoin for traditional MCT-based treatment improves clinical outcomes. MCT oil might be less effective in carnitine-acylcarnitine translocase deficiency patients compared with other FAODs and needs further investigation.
Sections du résumé
BACKGROUND
Patients with severe long-chain fatty acid oxidation disorders (LC-FAODs) experience serious morbidity and mortality despite traditional dietary management including medium-chain triglyceride (MCT)-supplemented, low-fat diets. Triheptanoin is a triglyceride oil that is broken down to acetyl-coenzyme A (CoA) and propionyl-CoA, which replenishes deficient tricarboxylic acid cycle intermediates. We report the complex medical and nutrition management of triheptanoin therapy initiated emergently for 3 patients with LC-FAOD.
METHODS
Triheptanoin (Ultragenyx Pharmaceutical, Inc, Novato, CA, USA) was administered to 3 patients with LC-FAOD on a compassionate-use basis. Triheptanoin was mixed with non-MCT-containing low-fat formula. Patients were closely followed with regular cardiac and laboratory monitoring.
RESULTS
Cardiac ejection fraction normalized after triheptanoin initiation. Patients experienced fewer hospitalizations related to metabolic crises while on triheptanoin. Patient 1 has tolerated oral administration without difficulty since birth. Patients 2 and 3 experienced increased diarrhea. Recurrent breakdown of the silicone gastrostomy tube occurred in patient 3, whereas the polyurethane nasogastric tube for patient 2 remained intact. Patient 3 experiences recurrent episodes of elevated creatine kinase levels and muscle weakness associated with illness. Patient 3 had chronically elevated C10-acylcarnitines while on MCT supplementation, which normalized after initiation of triheptanoin and discontinuation of MCT oil.
CONCLUSIONS
Triheptanoin can ameliorate acute cardiomyopathy and increase survival in patients with severe LC-FAOD. Substituting triheptanoin for traditional MCT-based treatment improves clinical outcomes. MCT oil might be less effective in carnitine-acylcarnitine translocase deficiency patients compared with other FAODs and needs further investigation.
Substances chimiques
Fatty Acids
0
Triglycerides
0
triheptanoin
2P6O7CFW5K
Carnitine
S7UI8SM58A
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
230-238Informations de copyright
© 2020 American Society for Parenteral and Enteral Nutrition.
Références
Vitoria I, Martin-Hernandez E, Pena-Quintana L, et al Carnitine-acylcarnitine translocase deficiency: experience with four cases in Spain and review of the literature. JIMD Rep. 2015;20:11-20.
Baruteau J, Sachs P, Broue P, et al. Clinical and biological features at diagnosis in mitochondrial fatty acid beta-oxidation defects: a French pediatric study of 187 patients. J Inherit Metab Dis. 2013;36(5):795-803.
Vockley J, Charrow J, Ganesh J, et al. Triheptanoin treatment in patients with pediatric cardiomyopathy associated with long chain-fatty acid oxidation disorders. Mol Genet Metab. 2016;119(3):223-231.
Roe CR, Brunengraber H. Anaplerotic treatment of long-chain fat oxidation disorders with triheptanoin: review of 15 years experience. Mol Genet Metab. 2015;116(4):260-268.
Vockley J, Marsden D, McCracken E, et al. Long-term major clinical outcomes in patients with long chain fatty acid oxidation disorders before and after transition to triheptanoin treatment-a retrospective chart review. Mol Genet Metab. 2015;116(1-2):53-60.
Vockley J, Burton B, Berry GT, et al. Results from a 78-week, single-arm, open-label phase 2 study to evaluate UX007 in pediatric and adult patients with severe long-chain fatty acid oxidation disorders (LC-FAOD). J Inherit Metab Dis. 2019;42(1)169*177.
Gillingham MB, Heitner SB, Martin J, et al. Triheptanoin versus trioctanoin for long-chain fatty acid oxidation disorders: a double blinded, randomized controlled trial. J Inherit Metab Dis. 2017;40(6):831-843.
Parini R, Invernizzi F, Menni F, et al. Medium-chain triglyceride loading test in carnitine-acylcarnitine translocase deficiency: insights on treatment. J Inherit Metab Dis. 1999;22(6):733-739.
Chalmers RA, Stanley CA, English N, Wigglesworth JS. Mitochondrial carnitine-acylcarnitine translocase deficiency presenting as sudden neonatal death. J Pediatr. 1997;131(2):220-225.
Minter Baerg MM, Stoway SD, Hart J, et al. Precision newborn screening for lysosomal disorders. Genet Med. 2018;20(8):847-854.
Margossian R, Schwartz ML, Prakash A, et al. Comparison of echocardiographic and cardiac magnetic resonance imaging measurements of functional single ventricular volumes, mass, and ejection fraction (from the Pediatric Heart Network Fontan Cross-Sectional Study). Am J Cardiol. 2009;104(3):419-428.