Long Chain Fatty Acid Oxidation Disorder (LCFAOD)


Long chain fatty acid oxidation disorder (LCFAOD) is the name given to a group of rare genetic diseases in which the patient’s body is unable to metabolize long chain fatty acids due to mutations in genes that encode for enzymes that are essential in this process. The disease leads to the accumulation of long chain fatty acids causing damage as well as energy deficiency.1

There is currently no cure for any type of LCFAOD, however, there are preventative measures that can ensure patients do not have a metabolic crisis or develop life-threatening comorbidities.

LCFAOD Consultations

LCFAOD is part of newborn screening programs in many countries. Different types of LCFAOD can be identified through newborn screening, including carnitine update defects, long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, trifunctional protein (TFP) deficiency, and very-long-chain acyl-coenzyme A (CoA) dehydrogenase (VLCAD) deficiency.2 

Following a positive newborn screening test, a consultation with the patient’s family should take place for further testing to reach a final diagnosis.  

During the consultation, the dietary interventions that are necessary, the necessity to avoid long periods of fasting as well as treatment options such as supplementation of medium-chain triglyceride oil should be discussed with the family. 

Genetic testing and counseling should also be offered to the parents and other family members of the patient that may be at risk of being carriers of an LCFAOD and passing the disease onto future generations.

LCFAOD Interventions 

The deficiency of one of the enzymes that are essential for the metabolism of long chain fatty acids means that these molecules can either not be transported into the mitochondria or oxidized once inside the mitochondria.

Cells use glucose as a primary source of energy, but in the absence of glucose such as during prolonged fasting or when energy demands are particularly high as in the case of intense exercise, fatty acid metabolism normally occurs to provide energy to cells.3 In the case of LCFAOD, fatty acid metabolism cannot take place and this can lead to a metabolic crisis, which can have catastrophic consequences including coma or death.

Metabolic crises can be prevented by avoiding long periods of fasting and intense exercise. Infants, ages 0 to 6 months with the disease, should be fed at least every 4 hours. For babies, ages 6 months to 3 years, the time between feeds can be increased to 8 hours. Patients, ages 3 and above should be able to tolerate fasting periods of 8 to 12 hours.4

Patients should have a low-fat snack before exercise and during long exercises. They should be given MCT oil 30 to 45 minutes before strenuous exercise and be supplemented with carbohydrates and fluids every 2 hours.4

LCFAOD Disorder Diet

Patients should follow a strict nutritional plan and consume a diet low in long chain fatty acids, which is supplemented with medium chain triglyceride to stop the attempted catabolism of fatty acids.5

The diet of infants with the disease should consist of medium-chain triglycerides (MCT), long chain fat, and supplements that provide 40% to 45% of the energy intake. In severe cases of the disease, long chain fats should be restricted to 10% and MCT to 30% of the energy intake while in moderate or mild cases, half of the fat calories should come from MCT and half from long chain fats. Around 15% of energy intake should come from proteins.6

In children older than age 1 and in adults, 10% to 20% of total energy intake should come from long chain fats and the rest comes from MCT.6

LCFAOD Medical Care

Triheptanoin (Dojolvi™) can be used as a calorie and fatty acid source for the treatment of children and adults with LCFAOD.7

In case of a metabolic crisis that requires hospitalization, 10% of intravenous dextrose should be administered promptly.8

LCFAOD Surgical Care

The accumulation of fatty acid inside cardiac cells can lead to cardiomyopathy. Cardiomyopathy can also be caused by low energy levels due to impaired fatty acid metabolism. In severe cases, patients may require surgery or a heart transplant.5 

LCFAOD Long-Term Monitoring

Patients with LCFAOD must be carefully monitored by a team of metabolic care providers who should work closely with their primary care physician. Their cardiac health should also be closely monitored using an echocardiogram (ECG) to ensure that they can receive adequate care as and when needed.1 

References

  1. Vockley J. Long-chain fatty acid oxidation disorders and current management strategies. Am J Manag Care. 2020;26(7 Suppl):S147-S154. doi:10.37765/ajmc.2020.88480
  2. Treatment of fatty acid oxidation disorders. March of Dimes. January 2014. Accessed June 20, 2021.
  3. Dhillon KK, Gupta S. Biochemistry, ketogenesis. Updated 2021 Feb 17. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Accessed June 24, 2021.
  4. Very long chain acyl CoA dehydrogenase deficiency (VLCADD) OMIM #201475. Genetic Metabolic Dietitians International. Accessed June 24, 2021.
  5. Merritt JL 2nd, MacLeod E, Jurecka A, Hainline B. Clinical manifestations and management of fatty acid oxidation disorders. Rev Endocr Metab Disord. 2020;21(4):479-493. doi:10.1007/s11154-020-09568-3
  6. Roe CR, Roe DS, Wallace M, Garritson B. Choice of oils for essential fat supplements can enhance production of abnormal metabolites in fat oxidation disorders. Mol Genet Metab. 2007;92(4):346-50. doi:10.1016/j.ymgme.2007.07.012
  7. Shirley M. Triheptanoin: first approval. Drugs. 2020;80(15):1595-1600. doi:10.1007/s40265-020-01399-5
  8. Very long chain acyl CoA dehydrogenase deficiency (LCAD). National Organization of Rare Disorders. 2020. Accessed June 24, 2021. 

Reviewed by Kyle Habet, MD, on 7/1/2021.

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