Pharmacological treatment, dietary approaches, and disease monitoring remain major challenges in the approach to patients with fatty acid oxidation disorders, as published in the World Journal of Hepatology. These and other topics were recently reviewed by Aathira Ravindranath and Moinak Sen Sarma, experts in pediatric gastroenterology.

Treatment recommendations for long chain fatty acid oxidation disorders (LCFAODs) are usually based on consensus by experts due to the lack of large-scale trials. Children with carnitine palmitoyltransferase 1 deficiency, a type of LCFAOD, should be given medium-chain triglycerides (MCT) supplementation. The recommended regimen is 2-3 g/kg/d during the first year and 1-1.25 g/kg/d thereafter.

“Diet rich in complex carbohydrates, low in fat with MCT and carnitine supplementation during well periods and intravenous glucose, night-time drip-feeding during crisis time will avoid the accumulation of toxic intermediaries,” Ravindranath and Sarma explained regarding carnitine shuttle defects, which also includes carnitine palmitoyltransferase 2 and carnitine-acylcarnitine translocase deficiencies.


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Treatment of very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency depends on disease severity:

  • Early onset severe form — intravenous glucose, MCT-based formula, and intensive care
  • Intermediate form — MCT supplementation (20% of total energy) and restriction of long-chain triglycerides (LCT) to 25%-30% of total energy
  • Myopathic form — pre-exercise MCT supplements (0.25 g/kg to 0.5 g/kg). Neither the administration of oral glucose before exercise nor the restriction of exercise are recommended

Read more about LCFAOD differential diagnosis

“Carnitine supplementation in VLCAD deficiency is controversial as it may increase the plasma flux of toxic acyl carnitine intermediates causing cardiac arrhythmias and rhabdomyolysis,” Ravindranath and Sarma said. Hence, they recommend starting carnitine supplementation only after the establishment of the diagnosis.

There are also emerging therapies, such as the peroxisome proliferator-activated receptor-alpha agonist bezafibrate, that should be considered in both carnitine shuttle defects and VLCAD deficiency. However, evidence suggests that it might not add value in the treatment of severe forms of VLCAD deficiency.

Another promising approach consists of using the ester form of hydroxybutyrate as the ketone body donor to improve exercise tolerance. However, the outcome of nutritional ketosis should be further studied.

Ravindranath and Sarma also highlighted several issues that should be addressed upon a suggestive diagnosis of VLCAD deficiency during a newborn screening:

  • The accuracy of the diagnostic test. A positive result on an high-sensitivity tandem mass spectrometry screen should be confirmed by enzyme assay in cultured fibroblasts or mutation analysis
  • The need for treatment in asymptomatic cases. They recommend to maintain breastfeeding if the levels of creatine phosphokinase (CPK) and transaminases are normal and to introduce high MCT, low LCT formula when the levels of CPK or transaminases are increased

Reference

Ravindranath A, Sarma M Sen. Mitochondrial hepatopathy: anticipated difficulties in management of fatty acid oxidation defects and urea cycle defects. World J Hepatol. 2022;14(1):180-194. doi:10.4254/wjh.v14.i1.180