Long Chain Fatty Acid Oxidation Disorder (LC-FAOD)

Long chain fatty acid oxidation disorder (LCFAOD) is a group of rare autosomal recessive genetic metabolic disorders characterized by impaired long chain fatty acid metabolism causing acute metabolic crises and energy deficiency.¹

There are 6 types of LCFAOD, each caused by mutations in genes encoding for enzymes involved in long chain fatty acid metabolism. These are carnitine palmitoyltransferase (CPT I or CPT II) deficiency, carnitine-acylcarnitine translocase (CACT) deficiency, very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency, long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) deficiency, and trifunctional protein (TFP) deficiency.²

Importance of Long Chain Fatty Acid Oxidation Disorder Patient Education

Patient education for any disease is very important because patients’ understanding of their own disease and its management can ensure better compliance with treatment and increase satisfaction with the care they receive. Patient education can also decrease healthcare providers’ liability. 

Finally, it can enhance patients’ self-care and self-esteem, as well as reduce anxiety and disruption in daily functioning.³

In the case of a genetic disease such as LCFAOD, patient education can allow patients and their families to seek genetic testing for diagnosis and carrier testing and to allow for early and appropriate treatment.

Invitae offers sponsored, free-of-charge genetic testing for people suspected of having LCFAOD in the US and Canada. The program is available for people who are suspected of having LCFAOD or have been diagnosed with LCFAOD and have had a plasma acylcarnitine test, even if the results were negative. Patients must complete the UltraCare Start Form for LCFAOD. The program tests for variants of 24 genes that are known to be associated with fatty acid beta-oxidation, carnitine shuttle, carnitine transport, ketogenesis, and other conditions that may lead to abnormal acylcarnitine test results. They are ACAD9, ACADM, ACADS, ACADSB, ACADVL, CPT1A, CPT2, ETFA, ETFB, ETFDH, FLAD1, HADH, HADHA, HADHB, HMGCL, HMGCS2, MLYCD, NADK2, SLC22A5, SLC25A20, SLC25A32, SLC52A1, SLC52A2, and SLC52A3.⁴

Newborn Screening for Long Chain Fatty Acid Oxidation Disorder

The management of LCFAOD mostly focuses on dietary interventions. Therefore, early diagnosis is very important.

Newborn screening tests for carnitine update defects, LCHAD deficiency, TFP deficiency, and VLCAD deficiency are available.⁵ Since its introduction, newborn screening for LCFAOD has dramatically improved outcomes in patients affected by the disease.⁶

Newborn screening can also allow a patient to enroll in a clinical trial for testing new potential treatments in development for LCFAOD.

Ultragenyx Pharmaceutical is currently running a LCFAOD online disease monitoring program with the aim to characterize the impact of the disease and its management and resource utilization to provide benefits to the LCFAOD community. It uses an online platform for participants or caregivers to self-report information. The developed database will be used to notify patients, caregivers, and patient advocacy groups of research studies and clinical trials.⁷

Long Chain Fatty Acid Oxidation Disorder Carrier Testing

All types of LCFAODs are caused by autosomal recessive mutations. So two people have a 25% risk of having a child affected by the disease if both are carriers of the same genetic mutation.⁸

Carrier testing can identify people who have a mutation in one of the genes that are known to be associated with LCFAODs.⁸ 

Prenatal genetic testing via amniocentesis or chorionic villus sampling and in vitro fertilization with preimplantation genetic testing can also be used to decrease the risk of having a child affected by the disease.⁹

These tests should be offered to couples with a known family history of LCFAODs. Genetic counseling should also be offered to carriers or families affected by the disease.¹⁰  

Available Patient Education Material

Ultragenyx Pharmaceutical has a website dedicated to patient advocacy that contains detailed information about LCFAOD, among other diseases. The website contains education and support resources about the diseases.¹¹

There is also an online resource FAOD in Focus specifically about fatty acid oxidation disorders, which contains information about signs, symptoms, and diagnosis of the disease. There are 2 versions of the website, 1 for patients and caregivers and 1 for healthcare professionals detailing the mechanisms of the disease, its impact, and information about genetic testing. Finally, the healthcare professional website contains downloadable resources that provide additional insight and support for patients, parents, and caregivers.^12,13

FOD Support is a national and international support group specifically for fatty acid oxidation disorders that offers a wealth of medical information and support resources for patients and families affected by these disorders. The group calls healthcare professionals to contribute their knowledge and expertise about fatty acid oxidation disorders.¹⁴ 

References

1. Vockley J, Burton B, Berry G, et al. Effects of triheptanoin (UX007) in patients with long-chain fatty acid oxidation disorders: results from an open-label, long-term extension study. J Inherit Metab Dis. 2021;44(1):253-263. doi:10.1002/jimd.12313
2. Knottnerus SJG, Bleeker JC, Wüst RCI, et al. Disorders of mitochondrial long-chain fatty acid oxidation and the carnitine shuttle. Rev Endocr Metab Disord. 19, 93–106 (2018). doi:10.1007/s11154-018-9448-1 
3. Fernsler JI, Cannon CA. The whys of patient education. Semin Oncol Nurs. 1991;7(2):79-86. doi:10.1016/0749-2081(91)90085-4
4. Long-chain fatty acid oxidation disorders. Invitae. Accessed June 25, 2021.
5. Treatment of fatty acid oxidation disorders. March of Dimes. Accessed June 25, 2021.
6. Marsden D, Bedrosian CL, Vockley J. Impact of newborn screening on the reported incidence and clinical outcomes associated with medium- and long-chain fatty acid oxidation disorders. Genet Med. 2021;23(5):816-829. doi:10.1038/s41436-020-01070-0
7. Long-chain fatty acid oxidation disorders online disease monitoring program. ClinicalTrials.gov. March 23, 2021. Updated April 19, 2021. Accessed June 25, 2021.
8. Merritt JL 2nd, Norris M, Kanungo S. Fatty acid oxidation disorders. Ann Transl Med. 2018;6(24):473. doi:10.21037/atm.2018.10.57
9. Rinaldo P, Studinski AL, Matern D. Prenatal diagnosis of disorders of fatty acid transport and mitochondrial oxidation. Prenat Diagn. 2001;21(1):52-4. doi:10.1002/1097-0223(200101)21:1<52::aid-pd973>3.0.co;2-h
10. Fatty Acid Oxidation Disorders Genetic Counseling. Inform. November 21, 2019. Accessed June 28, 2021.
11. Long-chain fatty acid oxidation disorders (LC-FAOD). Ultragenyx Pharmaceutical. Accessed June 25, 2021.
12. FAOD in Focus for patients and caregivers. Ultragenyx Pharmaceutical. Accessed June 25, 2021.
13. FAOD in Focus for US healthcare professionals. Ultragenyx Pharmaceutical. Accessed June 25, 2021.
14. FOD Support. Accessed June 25, 2021.

Article reviewed by Harshi Dhingra, MD, on July 1, 201.

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Ozge Ozkaya, MSc, PhD

Özge’s background is in research; she holds a MSc. in Molecular Genetics from the University of Leicester and a PhD. in Developmental Biology from the University of London. Özge worked as a bench scientist for six years in the field of neuroscience before embarking on a career in science communication. She worked as the research communication officer at MDUK, a UK-based charity that supports people living with muscle-wasting conditions, and then a research columnist and the managing editor of resource pages at BioNews Services before joining Rare Disease Advisor.