Dietary Management of the Ketogenic Glycogen Storage Diseases

Abstract The glycogen storage diseases (GSDs) comprise a group of rare inherited disorders of glycogen metabolism. The hepatic glycogenolytic forms of these disorders are typically associated with hypoglycemia and hepatomegaly. For GSD I, secondary metabolic disturbances include fasting hyperlactatemia, hyperuricemia, and hyperlipidemia. Glycogen storage disease III is caused by reduced activity of the debrancher enzyme, GSD VI by phosphorylase, and GSD IX by phosphorylase kinase. It has often been reported that the non-GSD I group of disorders have a benign course. However, myopathy, cardiomyopathy, and cirrhosis have been reported significant clinical morbidities associated with GSD III and IX in particular. There have been a range of reports indicating high-protein diets, high-fat diets, medium chain triglyceride (MCT), modified Atkins diet, and therapeutic ketones as rescuing severe phenotypes of GSD III in particular. The etiology of these severe phenotypes has not been defined. Cases presented in this report indicate potential harm from excessive simple sugar use in GSD IX C. Review of the literature indicates that most interventions have reduced the glycemic load and provide alternate substrates for energy in rescue situations. Prevention of complications is most likely to occur with a mixed balanced low glycemic index diet potentially with relative increases in protein.

Practical aspects of managing low protein diets.

Many inborn errors of metabolism can be successfully managed by restriction of natural protein intake, with or without special supplements. In some cases, there is a need for clear advice on management during metabolic crisis brought about by illness. Even when medical facilities and ongoing support are on hand, and special products are available and affordable, management of such conditions is challenging to families. Tailoring diet instruction to the needs and capabilities of the family is most likely to achieve success. Many Australian families cope better with simple guidelines aimed at reducing protein intake within the needs for growth and development and this style of management is also more likely to be successful in countries in which support is limited. Simple guidelines can take the form of increasing intake of certain types of foods and limiting others. Assessment of vitamin and mineral intake is however essential. Breastfeeding will provide less protein than standard infant formula, as well as immune protection, and needs to be encouraged and supported. Restricting meat and other high protein foods with increased intake of cereal and vegetable protein will still substantially decrease protein intake. Increasing intake of low protein vegetable sources or special low protein foods will also by default decrease protein intake. Families need specific guidelines for the care of their child when metabolic decompensation is a risk, with the aim of maintaining adequate energy intake, in forms that the child can eat or drink. A specialist pediatric dietitian can provide the expertise in formulating management plans appropriate for the family and facilities, with ongoing local management. The support of other families dealing with similar conditions can also be invaluable.