Approach
Treatment of GSD I involves providing a continuous dietary source of glucose to maintain euglycemia and to prevent acute and chronic complications as much as possible. Blood lactate increases rapidly when blood glucose decreases below the threshold for glucose counter-regulation (<72 mg/dL or 4.0 mmol/L). When hypoglycemia is prevented by providing an appropriate amount of glucose throughout the day and night, the biochemical abnormalities are ameliorated, liver size decreases, the tendency to bleeding is reversed, and growth improves.[13]
Hypoglycemic emergencies
Acute hypoglycemia is corrected by giving dextrose (intravenously or enterally). Once hypoglycemia is corrected, the dextrose infusion should continue to maintain euglycemia. Fluids containing 10% dextrose at or above a maintenance rate are usually sufficient for these infusions.[1] Unlike hypoglycemic emergencies in people with diabetes, glucagon should not be used.
Acute hypoglycemia should prompt investigations into other possible electrolyte or metabolic disturbances, particularly lactic acidosis.
Dietary carbohydrates
Dietary measures for patients with GSD I are based on two principles: reduce 'simple sugars’ (substrate reduction) and provide sufficient energy during the day (product supplementation).
Substrate reduction
The diet for patients with GSD I should be low in "simple sugars", including lactose/galactose and sucrose/fructose.[1]
Product supplementation
Various methods may be used to provide a continuous source of glucose at a rate sufficient to satisfy glucose requirements and to maintain euglycemia in the intervals between meals. They are given via the gastrointestinal tract by intragastric infusion (either nasogastric or gastrostomy tube) or by use of low-glycemic-index foods. Of these, uncooked cornstarch has the most suitable properties described to date. An estimation of the minimum amount of glucose required may be obtained by using the formula for calculating basal glucose production rate using the patient's ideal body weight. The precise amount of supplemental glucose or uncooked cornstarch and the schedule of administration must be determined empirically based on the results of clinical and biochemical monitoring.[14][15]
Infants should be fed frequently (variance between 1 to 3 hours) with a formula that does not contain either lactose or sucrose. The formula must contain a polymer of glucose (corn syrup solids or maltodextrins) that after digestion will yield a quantity of glucose equal to the calculated glucose production rate. If night-time feedings are a problem then continuous overnight feeding using the same formula may be given via a nasogastric or gastrostomy tube with the rate controlled by an infusion pump.[14][15]
Supplying uncooked cornstarch
Orally administered uncooked cornstarch acts as an intestinal reservoir of glucose that is slowly absorbed into the circulation. In many centers, uncooked cornstarch has replaced frequent daytime feedings of glucose or glucose polymers and overnight continuous intragastric infusion of glucose. It has been used successfully in infants as young as ages 8 months.[14][15][16] Although pancreatic amylase activity reaches adult levels at ages 2 to 4 years, it can be stimulated by starches. Careful exposure and dose increase can be attempted after ages 6 months, and has been successfully described at ages 1 to 2 years.[17]
Uncooked cornstarch is given as a slurry using water or artificially sweetened fluid, or in formula for infants, given at 3- to 5-hour intervals during the day and 4- to 6-hour intervals overnight. The amount given is determined by multiplying the time interval between feeds by the hourly glucose requirement for an ideal body weight. The optimum schedule and amounts of intermittent uncooked cornstarch feedings for patients of different ages is determined empirically by metabolic monitoring to ensure that biochemical goals are achieved. Careful consideration should be taken when choosing between continuous nocturnal gastric drip-feeding and nocturnal cornstarch regimen.[18]
An extended-release cornstarch preparation is available, which typically extends the duration of overnight fasting by 2 to 5 hours, so that some adults can maintain optimal metabolic control for up to 10 hours.[19] In addition to overnight use, extended-release cornstarch has increasingly been used during the day and in younger patients, both in daily practice and in a research setting. It is suitable for children from ages 2 years, but this may vary by country.
Macronutrients and micronutrients
Carbohydrate typically provides about 60% to 65% of the daily calories. Of the total daily calories, 30% to 45% is prescribed (both the amount and schedule) in the form of uncooked cornstarch. Most of the remaining dietary carbohydrate should ideally be low-glycemic-index starches. Protein should provide 10% to 15% of daily calories, with the remaining calories coming from fat.[1] Dietary fat should be restricted to about 20% of the total energy intake, equally distributed among monounsaturated, polyunsaturated, and saturated fats, and cholesterol intake restricted to <300 mg/day.
With the glucose requirements prescribed, the total caloric intake is determined largely by the patient's appetite, provided the rate of weight gain is not excessive. The dietitian must ensure that the patient is consuming an adequate amount of protein, fat, minerals, and vitamins to support optimal growth. When adequate glucose is prescribed to maintain euglycemia, milk products and fruit (despite their respective galactose and fructose content) may be used sparingly.[15]
Hyperuricemia
Hyperuricemia (reference ranges in children and adolescents: males 3.6 to 5.5 mg/dL; females 3.6 to 4.0 mg/dL) usually resolves when adequate exogenous glucose is provided. If hyperuricemia (>7 to 8 mg/dL) persists, allopurinol, a xanthine oxidase inhibitor, lowers serum uric acid to normal levels.
Hyperlipidemia
Hyperlipidemia should improve when adequate exogenous glucose is provided. Lipid-lowering agents (e.g., fenofibrate) are indicated when persistent severe hypertriglyceridemia, despite optimal glucose therapy, poses a significant risk of acute pancreatitis.[20] When plasma triglycerides exceed 1000 mg/dL (11.3 mmol/L), immediate lipid-lowering treatment is warranted. Treatment with fenofibrate should also be considered when optimal glucose therapy has not led to improvement and triglyceride values remain in the range 500 to 1000 mg/dL.
Liver transplantation
The long-term survival of pediatric patients following liver transplantation has markedly improved.[21] Liver transplantation should be considered when there is severe hepatic dysfunction or multiple adenomas deemed to be at high risk of undergoing malignant transformation.[1] Liver transplantation has the potential to significantly improve the quality of life for patients and their families so the risks and benefits versus the existing management for patients with GSD I must be weighed individually, and against the background of emergent new, innovative treatment options.[22][23]
Vitamin E supplementation
Vitamin E supplementation has been described to increase neutrophil count and improve their in vitro function, and is associated with decreased frequency and severity of infections in patients with GSD type Ib.[24]
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