Glycogen Storage Disease Type 1: Impact of Medium-Chain Triglycerides on Metabolic Control and Growth

Abstract

Background/Objective: Hypoketotic hypoglycaemia and hypertriglyceridaemia are biochemical hallmarks of glycogen storage disease (GSD) 1. Increased malonyl coenzyme A production which compromises oxidation of long-chain fatty acids via carnitine palmitoyltransferase (CPT) 1 inhibition plays a crucial role in the pathogenesis of these complications. Therapy consists primarily of nutritional support including frequent carbohydrate-rich meals. We studied the effect of a diet enriched in medium-chain triglycerides (MCT) on metabolic control/growth in GSD 1 as medium-chain fatty acids can be oxidised independently of CPT 1. Methods: An adult female, a 1.6-year-old boy with GSD 1a and a 6.5-year-old girl with GSD 1b treated with a classical GSD diet were enrolled; their ‘classical GSD diet’ was supplemented with MCT fats. Concentrations of glucose, lactate, ketone bodies triglycerides, uric acid, acylcarnitines in blood and organic acids in urine were determined. Results: No clinical or biochemical side-effects were observed. The MCT diet led to a decrease in uric acid concentrations in all patients. Triglyceride levels were reduced only in the youngest patient, while lactate concentrations did not significantly decrease. The MCT diet allowed for a reduction in carbohydrate and caloric intake required to maintain euglycaemia and led to improvement in growth in the two prepubertal patients. Conclusions: MCT supplementation had a positive effect on metabolic control and growth in our patients suffering from GSD 1.

Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics

“…109,110 The effect of medium-chain triglycerides on lowering cholesterol and triglycerides is currently being studied. 111,112 The use of vitamin E and its effectiveness in reducing the frequency of infection and improving neutropenia has been reported. 113 In conclusion, dietary therapy for the treatment of GSD I has improved the long-term outcomes for patients, but, unfortunately, many complications remain.…”

Lipids in hepatic glycogen storage diseases: pathophysiology, monitoring of dietary management and future directions

“…Several case reports describe the effects of medium chain triglycerides (MCT) in GSD I and III (Fernandes and Pikaar 1969; Cuttino et al 1970; Nagasaka et al 2007; Hanou et al 2008; Burns et al 2009; Das et al 2010; Bernstein et al 2010; El-Gharbawy et al 2014). In summary, laboratory parameters of metabolic control (triglyceride concentrations in GSD I; transaminases and CK in GSD III) decrease after MCT-supplementation, demonstrating that hyperlipidemia is carbohydrate-induced in GSD I.…”

Insulin‐resistance in glycogen storage disease type Ia: linking carbohydrates and mitochondria?

“…In this respect, medium-chain triglycerides (MCT) can undergo the liver FAO without the carnitine system and could theoretically overcome possible FAO defect. However, only a few studies have investigated the effect of MCT supplementation on metabolic balance in GSDI, showing increased free fatty acids levels, ACs levels and insulin/glucose ratio, raising concerns on its benefits (Das et al 2010;Nagasaka et al 2007).…”