MCT oil-based diet reverses hypertrophic cardiomyopathy in a patient with very long chain acyl-coA dehydrogenase deficiency

Abstract

Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency is one of the genetic defects of mitochondrial fatty acid beta-oxidation presenting in early infancy or childhood. If undiagnosed and untreated, VLCAD deficiency may be fatal, secondary to cardiac involvement. We assessed the effect of replacing part of the fat in the diet of a 2 ½-month-old male infant, who was diagnosed with VLCAD deficiency,with medium-chain triglyceride (MCT) oil and essential fats. The patient presented with vomiting, dehydration, and was found to have persistent elevation of liver function tests, hepatomegaly, pericardial and pleural effusion, right bundle branch block, and biventricular hypertrophy. Because of the cardiomyopathy, hepatomegaly, and an abnormal acylcarnitine profile and urine organic acids, he was suspected of having VLCAD deficiency. This was confirmed on acyl-coA dehydrogenase, very long chain (ACADVL) gene analysis. He was begun on an MCT oil-based formula with added essential fatty acids, uncooked cornstarch (around 1 year of age), and frequent feeds. By 7 months of age, cardiomyopathy had reversed and by 18 months of age, all cardiac medications were discontinued and hypotonia had improved such that physical therapy was no longer required. At 5 years of age, he is at the 50th percentile for height and weight along with normal development. Pediatricians need to be aware about the basic pathophysiology of the disease and the rationale behind its treatment as more patients are being diagnosed because of expansion of newborn screen. The use of MCT oil as a medical intervention for treatment of VLCAD deficiency remains controversial mostly because of lack of clear phenotype-genotype correlations, secondary to the genetic heterogeneity of the mutations. Our case demonstrated the medical necessity of MCT oil-based nutritional intervention and the need for the further research for the development of specific guidelines to improve the care of these patients.

De novo fatty acid biosynthesis and elongation in very long‐chain acyl‐CoA dehydrogenase‐deficient mice supplemented with odd or even medium‐chain fatty acids

“…VLCAD À/À in humans by reversing cardiomyopathy [18,19], and in mice by preventing the development of the muscular phenotype when applied as a bolus immediately prior to exercise [24]. As we previously observed that long-term application of MCTs induces a severe phenotype resembling metabolic syndrome [22], we hypothesize that most of the supplemented MCTs are elongated and accumulate as LCFAs.…”

“…All animal studies were performed with the approval of the University's Institutional Animal Care and Use Committee, and in accordance with the Committee's guidelines. Approval was given by the Regierungspr€ asidium Freiburg, Abteilung Landwirtschaft, L€ andlicher Raum, Veterin€ arund Lebensmittelwesen (File number: .81/G- [14][15][16][17][18][19][20].…”

Recurrent ACADVL molecular findings in individuals with a positive newborn screen for very long chain acyl-coA dehydrogenase (VLCAD) deficiency in the United States

“…One possibility for this high apparent carrier rate is that the second pathogenic allele was missed by Sanger sequence analysis. We could find at least one example in the literature of a patient with a large deletion in ACADVL who was missed by Sanger sequence analysis [24]. Alternatively, variants affecting deep intronic or promoter sequence may also be missed by the Sanger analysis we provide.…”

Orphan drugs in development for long-chain fatty acid oxidation disorders: challenges and progress

“…37 MCT supplementation has been associated with a reversal of cardiomyopathy in case reports of patients with CACT and VLCAD deficiency. 28,38,39 However, reports have noted that even highly compliant VLCAD patients still had significant muscle weakness, muscle pain, or myoglobinuria. 17 Although secondary carnitine deficiency is common in the LCFAO disorders, carnitine supplementation is controversial.…”