Optimal dietary therapy of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency

Abstract

Current dietary therapy for long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiency consists of fasting avoidance, and limiting long-chain fatty acid (LCFA) intake. This study reports the relationship of dietary intake and metabolic control as measured by plasma acylcarnitine and organic acid profiles in 10 children with LCHAD or TFP deficiency followed for 1 year. Subjects consumed an average of 11% of caloric intake as dietary LCFA, 11% as MCT, 12% as protein, and 66% as carbohydrate. Plasma levels of hydroxypalmitoleic acid, hydroxyoleic, and hydroxylinoleic carnitine esters positively correlated with total LCFA intake and negatively correlated with MCT intake suggesting that as dietary intake of LCFA decreases and MCT intake increases, there is a corresponding decrease in plasma hydroxyacylcarnitines. There was no correlation between plasma acylcarnitines and level of carnitine supplementation. Dietary intake of fat-soluble vitamins E and K was deficient. Dietary intake and plasma levels of essential fatty acids, linoleic and linolenic acid, were deficient. On this dietary regimen, the majority of subjects were healthy with no episodes of metabolic decompensation. Our data suggest that an LCHAD or TFP-deficient patient should adhere to a diet providing age-appropriate protein and limited LCFA intake (10% of total energy) while providing 10-20% of energy as MCT and a daily multi-vitamin and mineral (MVM) supplement that includes all of the fat-soluble vitamins. The diet should be supplemented with vegetable oils as part of the 10% total LCFA intake to provide essential fatty acids.

Effect of optimal dietary therapy upon visual function in children with long-chain 3-hydroxyacyl CoA dehydrogenase and trifunctional protein deficiency

“…We previously reported that the concentration of plasma hydroxyacylcarnitines is related to the dietary fat intake of children with LCHAD deficiency [7]. Dietary long-chain fat intake was positively correlated and dietary MCT intake was negatively correlated with plasma hydroxyacylcarnitine concentration in 10 patients.…”

“…Plasma hydroxylated acylcarnitine metabolites are closely correlated to plasma levels of the corresponding free hydroxylated fatty acids [7,28,29]. Others have speculated that the carnitine ester may be detoxifying and the free hydroxylated acid may be toxic but no data to support or refute that speculation has been published.…”

“…There was no DHA consumed in the diet; the sole source of DHA was from the supplement. A more detailed analysis of the nutritional intake of 10 of these subjects has been published elsewhere [7].…”

“…Therapy for LCHAD deficiency includes fasting avoidance and consumption of a diet low in long chain fatty acids (LCFA), but supplemented with medium-chain triglycerides (MCT). This approach minimizes LCFA oxidation as evidenced by low plasma long-chain 3-hydroxyacylcarnitine profiles [7].…”

Growth in Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency

“…The diet, low in fat content and hence longchain fatty acids from normal food, is supplemented with medium-chain triglycerides (MCT fat) and thereby bypasses the enzymatic defect. Supplementation with essential fatty acids is necessary to avoid deficiency (Gillingham et al 1999;Gillingham et al 2003;Spiekerkoetter et al 2009a); however, management may vary considerably (Potter et al 2012). To inhibit lipolysis, frequent feeds are necessary.…”