Format

Send to

Choose Destination
Mol Genet Metab. 2016 Nov;119(3):223-231. doi: 10.1016/j.ymgme.2016.08.008. Epub 2016 Aug 27.

Triheptanoin treatment in patients with pediatric cardiomyopathy associated with long chain-fatty acid oxidation disorders.

Author information

1
Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA. Electronic address: vockleyg@upmc.edu.
2
Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
3
Cooper University, Camden, NJ, USA.
4
Sutter Medical Center, Sacramento, CA, USA.
5
Mt. Sinai School of Medicine, New York, NY, USA.
6
Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA.
7
Children's Hospital of Michigan, Detroit, MI, USA.
8
Lucile Packard Children's Hospital Stanford, Palo Alto, CA, USA.
9
Children's Hospital of Orange County, Orange, CA, USA.
10
Ultragenyx Pharmaceutical, Inc., Novato, CA, USA.

Abstract

Long-chain fatty acid oxidation disorders (LC-FAOD) can cause cardiac hypertrophy and cardiomyopathy, often presenting in infancy, typically leading to death or heart transplant despite ongoing treatment. Previous data on triheptanoin treatment of cardiomyopathy in LC-FAOD suggested a clinical benefit on heart function during acute failure. An additional series of LC-FAOD patients with critical emergencies associated with cardiomyopathy was treated with triheptanoin under emergency treatment or compassionate use protocols. Case reports from 10 patients (8 infants) with moderate or severe cardiomyopathy associated with LC-FAOD are summarized. The majority of these patients were detected by newborn screening, with follow up confirmatory testing, including mutation analysis; all patients were managed with standard treatment, including medium chain triglyceride (MCT) oil. While on this regimen, they presented with acute heart failure requiring hospitalization and cardiac support (ventilation, ECMO, vasopressors) and, in some cases, resuscitation. The patients discontinued MCT oil and began treatment with triheptanoin, an investigational drug. Triheptanoin is expected to provide anaplerotic metabolites, to replace deficient TCA cycle intermediates and improve effective energy metabolism. Cardiac function was measured by echocardiography and ejection fraction (EF) was assessed. EF was moderately to severely impaired prior to triheptanoin treatment, ranging from 12-45%. Improvements in EF began between 2 and 21days following initiation of triheptanoin, and peaked at 33-71%, with 9 of 10 patients achieving EF in the normal range. Continued treatment was associated with longer-term stabilization of clinical signs of cardiomyopathy. The most common adverse event observed was gastrointestinal distress. Of the 10 patients, 7 have continued on treatment, 1 elected to discontinue due to tolerability issues, and 2 patients died from other causes. Two of the case histories illustrate that cardiomyopathy may also develop later in childhood and/or persist into adulthood. Overall, the presented cases suggest a therapeutic effect of triheptanoin in the management of acute cardiomyopathy associated with LC-FAOD.

KEYWORDS:

Cardiomyopathy; Fatty acid oxidation disorders; Metabolic disorders; Triheptanoin

PMID:
27590926
PMCID:
PMC5083220
DOI:
10.1016/j.ymgme.2016.08.008
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center