Effects of higher dietary protein intake on energy balance and metabolic control in children with long-chain 3-hydroxy acyl-CoA dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiency

Abstract

The incidence of overweight and obesity is increasing among children with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) or mitochondrial trifunctional (TFP) deficiency. Traditional treatment includes fasting avoidance and consumption of a low-fat, high-carbohydrate diet. A diet higher in protein and lower in carbohydrate may help to lower total energy intake while maintaining good metabolic control. To determine the short-term safety and eYcacy of a high protein diet, subjects were admitted to the General Clinical Research Center and fed an ad-libitum highprotein diet and a high-carbohydrate diet for 6 days each using a randomized, crossover design. Nine subjects with LCHAD or TFP deficiency, age 7-14 were enrolled. Body composition was determined by DEXA. Total energy intake was evaluated daily. Resting energy expenditure and substrate utilization were determined by indirect calorimetry. Post-prandial metabolic responses of plasma glucose, insulin, leptin, ghrelin, acylcarnitines, and triglyceride were determined in response to a liquid meal. Subjects had a higher fat mass, lower lean mass and higher plasma leptin levels compared to reference values. While on the high protein diet energy consumption was an average of 50 kcals/ day lower (p=0.02) and resting energy expenditure was an average of 170 kcals/day higher (p=0.05) compared to the high carbohydrate diet. Short-term higher protein diets were safe, well tolerated, and resulted in lowered energy intake and increased energy expenditure than the standard highcarbohydrate diet. Long-term studies are needed to determine whether higher protein diets will reduce the risk of overweight and obesity in children with LCHAD or TFP deficiency.

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

“…This indicates that overweight/obesity was overrepresented in our cohort. Analogous to our findings, Gillingham et al show an obesity rate of 30 % in nine children with LCHAD deficiency (Gillingham et al 2007), while Lund et al do not report the weight development of their patients (Lund et al 2010). It is noteworthy that the severe lipid restriction results in a relatively high carbohydrate content which is interesting from an overweight/obesity perspective.…”

“…A rapid weight gain in infancy may also cause insulin resistance (Dunger et al 2005). To the best of our knowledge, insulin sensitivity has not been studied in LCHAD-deficient patients, although one study suggests that children with LCHAD/MTP-deficiency and adiposity have normal insulin sensitivity based on normal insulin secretion (Gillingham et al 2007). Three out of five patients reached FH within 1 SDS of TH and mean FH was -0.6 SDS (girls)/0.4 SDS (boys), which indicated adequate growth in the majority of patients.…”

Genetic determinants of hepatic steatosis in man

“…Liver histology reveals abundant microvesicular fat, supporting the concept of a mitochrondrial defect in the ␤ oxidation pathway ( 140 ). Children with LCHAD and TFP defi ciency have a high incidence of obesity (30%) as defi ned by a BMI у 95% for age ( 141 ). free fatty acids occurs through a variety of enzymes, including adipocyte triglyceride lipase (ATGL or PNPLA2).…”

Successful Weight Loss in Two Adult Patients Diagnosed with Late-Onset Long-Chain Fatty Acid Oxidation Defect

“…Patients who cannot tolerate fasting and are restricted in their physical activity, for example, patients with long-chain fatty acid oxidation defect (LCFAOD) have an increased risk for obesity. The prescribed diet therapy for these patients is mostly experience-based (Spiekerkoetter et al 2009(Spiekerkoetter et al , 2010Gillingham et al 2007;Laforêt and Vianey-Saban 2010). Experts advise avoidance of catabolic situations and discourage weight reduction in these patients (Gillingham et al 2007).…”

“…The prescribed diet therapy for these patients is mostly experience-based (Spiekerkoetter et al 2009(Spiekerkoetter et al , 2010Gillingham et al 2007;Laforêt and Vianey-Saban 2010). Experts advise avoidance of catabolic situations and discourage weight reduction in these patients (Gillingham et al 2007). Since obesity brings new health risks, we face a growing demand for weight reduction in LCFAOD patients.…”