Long-term experience with triheptanoin in 12 Austrian patients with long-chain fatty acid oxidation disorders

Abstract

Background Long-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. Methods We 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 patients Results For 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 1.2–15.7) 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. Conclusion In 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 for the treatment of long‐chain fatty acid oxidation disorders: Final results of an open‐label, long‐term extension study

“…The reductions in the annualized rate and duration of MCEs were consistent with the results from the CL201 study 8,9 in triheptanoinnaïve patients (we also noted improvements in episodes and hospitalizations with triheptanoin compared with the CL201 study) and with reports of sustained efficacy reported in retrospective studies of triheptanoin, 4,19 including long-term triheptanoin treatment up to 16-19 years. 20,21 These encouraging results are important for clinicians and patients with LC-FAOD considering treatment with triheptanoin. In the interim analysis, there was a reduction in annualized total MCE event rate (70% median reduction) and duration (80% median reduction) in the triheptanoin-naïve group, with a mean study duration of 15.7 months.…”

Lipidomic and Proteomic Alterations Induced by Even and Odd Medium-Chain Fatty Acids on Fibroblasts of Long-Chain Fatty Acid Oxidation Disorders

“…In particular, C7 resulted in a higher ratio also for the species 40:2 of CER/HEX and for 42:1 of SM/HEX ( Figure 5 E,F). It is therefore conceivable that C7 may improve neuropathic symptoms via remodeling of complex lipids [ 31 , 32 , 33 , 34 ]. On the other hand, C8 showed a similar effect on the ratio for the species 34:1; however, all other species remained unaffected ( Figure 5 E,F).…”