Glycogen storage disease type I medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2]

Overview

The medical management of glycogen storage disease type 1 (GSD type 1) is divided into nutritional therapy and pharmacologic management of systemic complications. The primary concern in infants and young children with GSD type 1 is hypoglycemia. Small frequent feeds high in complex carbohydrates (preferably those high in fiber) are administered at regular intervals throughout 24 hours for the prevention of hypoglycemia. Sucrose (fructose and glucose) and lactose (galactose and glucose) may be limited or avoided. Solid food is introduced at the time of 4 - 6 months. Infant cereals are started followed by vegetables and then by meat.The preferred treatment for young child is cornstarch (CS); which may be used alone or by mixing it with sucrose-free, fructose-free, lactose-free infant formula, sugar-free soy milk, sugar-free drinks, and/or water. Other treatment strategies are directed towards management of hypocitraturia, hypercalcemia, proteinuria, platelet dysfunction, and neutropenia.

Medical Therapy

The medical management of glycogen storage disease type 1 (GSD type 1) is divided into nutritional therapy and pharmacologic management of systemic complications.

• The primary concern in infants and young children with GSD type 1 is hypoglycemia.
• So, the first line treatment for GSD type 1 is the prevention of hypoglycemia.
• Small frequent feeds high in complex carbohydrates (preferably those high in fiber) are distributed evenly throughout 24 hours for the prevention of hypoglycemia.
• A metabolic dietician should be consulted once a case of GSD type 1 is diagnosed.
• Distribution of calories:
  • Calories from carbohydrate: 60-70%
  • Calories from protein: 10-15%
  • Calories from fats: Remaining calories (<30% for children older than 2 years)
• Sucrose (fructose and glucose) and lactose (galactose and glucose) may be limited or avoided.
• Good metabolic control help to prevent complications in patients with GSD type 1.

Nutritional Therapy

• 1. Infants
  • 1.1 Formula and enteral feedings
    • 1.1.1 Infant sleep <3-4 hours
      • Preferred treatment (1): Soy-based formula, fed on demand q2h – q3h
      • Preferred treatment (2): Sugar-free formula, fed on demand q2h – q3h
      • Preferred treatment (3): A formula that is free of sucrose, fructose, and lactose; fed on demand q2h – q3h
    • 1.1.2 Infant sleep >3-4 hours
      • Preferred treatment (1): Overnight gastric feedings (OGFs)
      • Preferred treatment (2): Wake up infant q3h - q4h; monitor blood glucose and offer feeding

      Note (1): As hypoglycemia in GSD type 1 can be life-threatening and may cause seizures, permanent brain damage and even death, training of the parents (and/or child, when older) in inserting a nasogastric (NG) tube or that a G-tube be surgically placed is recommended, so that there is always access to treat for hypoglycemia, especially during times of illness or refusal to eat.

      Note (2): A G-tube may not be a good option in patients of GSD type 1b with neutropenia as it increases the risk of recurrent infections at the surgical site. Granulocyte colony-stimulating factor (G-CSF or Neupogen) should be administered before placing a G-tube if the child has neutropenia.

      Note (3): Blood glucose level should be maintained at more than 70 mg/dl or 4 mmol/l.

      Note (4): Feeding regimen are decided on a case by case basis.

      Note (5): The rate of the continuous tube feeding should be calculated to provide a glucose infusion rate of:

      • In infancy: 8–10 mg glucose/kg/min
      • In older children: 4–8 mg glucose/kg/min

      Note (6): Infant should be immediately fed after discontinuing tube feedings in order to avoid a rapid decrease in blood glucose due to high circulating insulin levels.

      Note (7): It is advisable to use safety precautions such as bed-wetting devices (to detect formula spilling onto the bed), infusion pump alarms, safety adapters, connectors, and tape for tubing to detect pump failure and occluded or disconnected tubing. These events may lead to hypoglycemia, seizures, and even death.

  • 1.2 Introducing solid food

    Note (1): Introduced at the time of 4 - 6 months. Infant cereals are started followed by vegetables and then by meat.

    Note (2): Fruits, juice, and other sucrose-containing, fructose-containing, and lactose-containing foods are limited or avoided.

• 2. Young child

  • Preferred treatment (1): Cornstarch (CS) - 1.6 g of CS/Kg of body weight q3h - q4h for young children, and 1.7–2.5 g CS/kg q4h - q5h (sometimes q6h) for older children, adolescents, and adults.

  Note (1): CS may also be used by mixing it with sucrose-free, fructose-free, lactose-free infant formula, sugar-free soy milk, sugar-free drinks, and/or water.

  Note (2): Optimal nutrition at a young age may help prevent or delay some of the long-term complications of the disease. Therefore, the focus of the diet must exceed simply preventing and treating hypoglycemia. The following table summarizes the food allowed and foods not allowed in GSD type 1.

Food group	Foods allowed	Foods not allowed
Dairy	Limited to one serving per day: 1 cup low-fat milk (ideally soy or almond milk) 1 cup low-fat sugar-free yogurt 1.5 oz. hard cheese	Ice cream Sweetened yogurt with milk Sweetened milk
Cereals	Dry and cooked cereals with no added sugar	Cereals with fruit or sugar added
Breads	White, wheat, or rye bread Crackers, matzo English muffins Dinner rolls, biscuits Pita bread	Rasin bread Muffins Sweet rolls Pies Cakes Sweet bread Waffles and pancakes made with sugar
Starches	Brown and white rice Pasta Popcorn Tortillas White potatoes	Any starches with sugar added Sweet potatoes
Vegetables	All nonstarchy vegetables including: Asparagus Cabbage Spinach Squash Onions Green beans Turnips Greens	Any vegetables with added sugar, milk, and cheese Corn, peas, and carrot have more sugar than the others
Fruits	Lemons and limes Avocados	All other fresh, canned, and dried fruits Tomatoes
Meat	Lean poultry Beef Pork Fish	Organ meat Fatty and processed meat
Legumes or nuts	All beans and nuts	Any beans, nuts, or seeds with sugar added
Soups	Borth soups made with allowed meats, starches, and vegetables	Creamed soups
Fats	Canola and olive oils Corn, safflower, canola, and soybean oil-based condiments	Trans fatty acids Saturated fats
Sweets	Sugar substitutes, sucralose Dextrose 100% Corn syrup, rice syrup Sugar-free jell-O and pudding Candies made with dextrose	All other sugars, sweets, syrups, high-fructose corn syrup, honey, molasses, sorbitol, and cane sugar; juice, and syrups
Adapted from Genetics in Medicine

Therapeutic strategies for renal tubular dysfunction

• 1. Treatment of Hypocitraturia
  • 1.1 Oral citrate supplementation
    • 1.1.1 Young children
      • Preferred treatment (1): Liquid potassium citrate 1 mEq/kg q24h in three divided doses
    • 1.1.2 Older children and adults
      • Preferred treatment (1): Potassium citrate tablets 10 mEq q24h in three divided doses

      Note (1): Citrate should be used cautiously and monitored as it may cause hypertension and hyperkalemia. Hyperkalemia can be life-threatening in the setting of renal impairment.

• 2. Treatment of Hypercalciuria
  • 2.1 Thiazide diuretics
    • 1.1.1 Young children
      • Preferred treatment (1): Chlorthalidone (liquid preparation)
    • 1.1.2 Older children and adults
      • Preferred treatment (1): Hydrochlorothiazide (tablets)

      Note (1): Interval urinary calcium-to-creatinine ratios are used to monitor the efficacy of therapy.

• 3. Treatment of Proteinuria

  • Preferred treatment (1): Angiotensin receptor blocker
  • Preferred treatment (2): Angiotensin converting enzyme inhibitor

Therapeutic strategies for platelet dysfunction

• 1. Treatment of platelet dysfunction/von Willebrand disease
  • 1.1 Antifibrinolytics
    • 1.1.1 For oral hemorrhage
      • Preferred treatment (1): ɛ-aminocaproic acid (Amicar), “swish for 30 seconds and spit” 1.25 g q6h
    • 1.1.2. For more severe mucosal-associated bleeding
      • Preferred treatment (1): ɛ-aminocaproic acid (Amicar), an i.v. bolus of 4 g in 250 ml of D5W/NS infused over 1 hour followed by a drip of 1 g/h (50 ml/h) for 8 hours or until bleeding is controlled is needed.
      • Alternative treatment (1): ɛ-aminocaproic acid (Amicar), PO 5g in first hour, followed by 1 g/h orally for 8 h or until hemorrhage is controlled (if i.v. form is unavailable).

      Note (1): Contraindications of Amicar include individuals with disseminated intravascular coagulation and if activated prothrombin complex concentrate (FEIBA) has been used.

      Note (2): Absence of genitourinary tract bleeding should be ensured as inhibition of fibrinolysis may lead to an obstructive nephropathy.

  • 1.2 Vasopressin analogues

    • Preferred treatment (1): Deamino-8-D-arginine vasopressin (DAVPP)

    Note (1): Deamino-8-D-arginine vasopressin (DDAVP) administration carries the risk of fluid overload and hyponatremia in the setting of i.v. glucose administration and must be used with caution in GSD type 1 patients.

Therapeutic strategies for neutropenia

• 1. Treatment of neutropenia
  • 1.1 Granulocyte colony stimulating factor (G-CSF)

    • Preferred treatment (1): G-CSF (Neupogen) SC 1.0 μg/kg q24h daily or every other day

  • 1.2 Antioxidants

    • Preferred treatment (1): Vitamin E supplementation