Dietary lipids in glycogen storage disease type III: A systematic literature study, case studies, and future recommendations

Abstract

Summary A potential role of dietary lipids in the management of hepatic glycogen storage diseases (GSDs) has been proposed, but no consensus on management guidelines exists. The aim of this study was to describe current experiences with dietary lipid manipulations in hepatic GSD patients. An international study was set up to identify published and unpublished cases describing hepatic GSD patients with a dietary lipid manipulation. A literature search was performed according to the Cochrane Collaboration methodology through PubMed and EMBASE (up to December 2018). All delegates who attended the dietetics session at the IGSD2017, Groningen were invited to share unpublished cases. Due to multiple biases, only data on GSDIII were presented. A total of 28 cases with GSDIII and a dietary lipid manipulation were identified. Main indications were cardiomyopathy and/or myopathy. A high fat diet was the most common dietary lipid manipulation. A decline in creatine kinase concentrations ( n = 19, P < .001) and a decrease in cardiac hypertrophy in paediatric GSDIIIa patients ( n = 7, P < .01) were observed after the introduction with a high fat diet. This study presents an international cohort of GSDIII patients with different dietary lipid manipulations. High fat diet may be beneficial in paediatric GSDIIIa patients with cardiac hypertrophy, but careful long‐term monitoring for potential complications is warranted, such as growth restriction, liver inflammation, and hepatocellular carcinoma development.

Data highlighting effects of Ketogenic diet on cardiomyopathy and hepatopathy in Glycogen storage disease Type IIIA

“…At that time she was introduced a high carbohydrates diet (frequent diurnal and nocturnal cornstarch meals); carbohydrates (9 g/kg per day (g/kg/d)) contributed 53% daily calories, proteins (4 g/kg/d) contributed 23% and fats (1.8 g/kg/d) contributed another 23%, according to the recommendations [2] . Progressively she developed left ventricular obstructive hypertrophy, hepatomegaly and skeletal myopathy with highly elevated liver and muscle enzymes, as previously reported [3] , [4] , [5] , [6] . She also presented recurrent hypoglycemic events despite treatment with frequent diurnal and nocturnal meals with cornstarch supplements.…”

Beneficial Effects of Modified Atkins Diet in Glycogen Storage Disease Type IIIa

“…Rossi et al [5] and many other authors have shown the cardiac pathology of GSD IIIa to benefit from high-fat diet [5,18,19]. The median duration of diet in the study of of Rossi et al [5] was 18 months, which is longer than that in the present report. In our study group, 2 patients with hypertrophic cardiomyopathy had carried on MAD for a relatively short period of time (5-7 months), and no apparent differences between cardiac parameters were observed.…”

Normalization of obstructive cardiomyopathy and improvement of hepatopathy on ketogenic diet in patient with glycogen storage disease (GSD) type IIIa

“…In both patients, CK levels in blood decreased, cardiomyopathy improved and associated symptoms disappeared [ 6 ]. Furthermore, a recent cohort study by Rossi et al reveals a decrease of CK levels in 89% of patients with GSD type IIIa treated with high fat diet [ 7 ]. Francini-Pesenti et al report on a 34 years-old patient with GSD type IIIa with hypertrophic cardiomyopathy who was also treated with a MAD.…”

“…Regarding hepatopathy, Rossi et al also report a decrease of ALT and AST concentrations in adults in 100% and 83% patients, respectively. In children, ALT and AST decrease in only 11% and 22% patients, respectively [ 7 ]. An improvement of ALT and AST levels is reported by Brambilla (AST of 21% and 72%; ALT of 6 and 38%) and Francini-Pesenti (AST of 29% and ALT of 24%), but they do not report any change in liver sizes [ 6 , 8 ].…”

“…Development of the cardiomyopathy in GSD type IIIa may be caused by the high carbohydrate diet, according to reports of the literature about the association between carbohydrate overtreatment and an elevated risk for cardiac involvement and/or cardiomyopathy [ 1 ]. Rossi et al reports that an early switch to a high fat diet decreases cardiac glycogen storage, probably caused by lower carbohydrate intake and fat properties [ 7 ]. Furthermore, it is hypothesized that elevated levels of insulin, generated by a high carbohydrate diet, activate glycogen synthase and promote glycogen storage in myocytes and lipolysis inhibition [ 5 ].…”