Long-term Experience with Triheptanoin in 12 Austrian Patients with Long-chain Fatty Acid Oxidation Disorders

Abstract

BackgroundLong-chain fatty acid oxidation disorders (LC-FAOD) are a group of rare inborn errors of metabolism with autosomal recessive inheritance that may cause life-threatening events. Treatment with triheptanoin, a synthetic seven-carbon fatty acid triglyceride compound with an anaplerotic effect, seems beneficial, but clinical experience is limited. We report our long-term experience in an Austrian cohort of LC-FAOD patients.MethodsWe retrospectively assessed clinical outcome and total hospitalization days per year before and after start with triheptanoin by reviewing medical records of 12 Austrian LC-FAOD patientsResultsFor 12 Austrian LC-FAOD patients at three metabolic centers, triheptanoin was started shortly after birth in 3/12, and between 7.34 and 353.3 (median 44.5; mean 81.1) months of age in 9/12 patients. For 11 pediatric patients, mean duration of triheptanoin intake was 5.3 (median 3.9, range 1.2 to 15.7) years, 10/11 pediatric patients have an ongoing intake of triheptanoin. One patient quit therapy due to reported side effects. Total hospitalization days per year compared to before triheptanoin treatment decreased by 82.3% from 27.1 (range 11-65) days per year to 4.8 (range 0-13) days per year, and hospitalization days in the one year pre- compared to the one year post-triheptanoin decreased by 69.8% from 27.1 (range 4-75) days to 8.2 (range 0-25) days. All patients are in good clinical condition, show normal psychomotor development and no impairment in daily life activities.ConclusionIn this retrospective observational study in an Austrian LC-FAOD cohort, triheptanoin data show improvement in disease course. Triheptanoin appears to be a safe and beneficial treatment option in LC-FAOD. For further clarification, additional prospective randomized controlled trials are needed.

The Pharmacokinetics of Triheptanoin and Its Metabolites in Healthy Subjects and Patients With Long‐Chain Fatty Acid Oxidation Disorders

“…6,7 Furthermore, triheptanoin has been studied clinically over 13 years, and the available literature provides clinical responses associated with LC-FAODs. [8][9][10][11][12][13] Triheptanoin is extensively hydrolyzed into glycerol and heptanoate (C7 fatty acids) in the gastrointestinal (GI) tract by pancreatic lipases, and subsequently, heptanoate is absorbed through the gut wall. 14 Heptanoate can diffuse across the mitochondrial membranes and undergo a series of beta-oxidative metabolic reactions to generate acetyl coenzyme A (CoA) and propionyl-CoA, bypassing the carnitine shuttle and long-chain fatty acid oxidation enzymes that are deficient in patients with LC-FAODs.…”

Genetic, biochemical, and clinical spectrum of patients with mitochondrial trifunctional protein deficiency identified after the introduction of newborn screening in the Netherlands

“…Recent studies suggest a beneficial effect of treatment with beta-hydroxybutyrate and triheptanoin in patients with (long-chain) fatty acid oxidation disorders. [30][31][32][33] The reported LCKATD patient, who was treated with sodium-D,L-3-hydroxybutyrate, had a longer survival time than LCKATD patients previously reported in the literature and potentially benefited from this treatment. However, both treatment strategies require tolerance for enteral feeding, which is a sometimes unavoidable obstacle in the treatment of critically ill patients.…”

“…This implies that the currently available treatment options are insufficient and improved treatment strategies are needed. Recent studies suggest a beneficial effect of treatment with beta‐hydroxybutyrate and triheptanoin in patients with (long‐chain) fatty acid oxidation disorders 30–33 . The reported LCKATD patient, who was treated with sodium‐D,L‐3‐hydroxybutyrate, had a longer survival time than LCKATD patients previously reported in the literature and potentially benefited from this treatment.…”

Triheptanoin in the management of long-chain fatty acid oxidation disorders: a profile of its use

“…A retrospective observational study in an Austrian cohort of 8 paediatric patients with LC-FAOD treated with triheptanoin found that total hospitalization days/year decreased from a mean 27.1 days /year in the year prior to initiating triheptanoin treatment to a mean 8.2 days/year in the year after starting treatment [14].…”