GSD Type 1

Other Names    Von Gierke disease

Defect:

Ia    deficiency in glucose-6-phosphatase(G6Pase)
Ib    deficiency  in  glucose-6-phosphatase(G6Pase) transporter, which results in inability of G6Pase to reach its place of action inside the cell.
Ic    defect in macrosomal phosphate or pyrophosphate transport.
Id    is a macrosome defect in glucose transport


Signs & Symptoms (GSD Ia)

  • Severe hypoglycemia within 3-4 hours after a meal.
  • Symptomatic hypoglycemia may appear soon after birth, but most children do not present this until age 3-6 months when feeds are being spaced.
  • Enlarged liver causing protruding abdomen.
  • Long term complications manifest as hepatic adenomas (liver tumors); renal (kidney) problems such as scarring of the kidney’s filters (glomerulosclerosis), renal tubular dysfunction, kidney stones and osteoporis.

Signs & Symptoms (GSD Ib)

All the S/Sx of GSD Ia
Neutropenia – low levels of neutrophil ( a type of white blood cell that ingest bacteria) thereby  making  the
body vulnerable to bacterial and fungal infections.
Inflammatory bowel disease

Causes    Inherited autosomal-recessive manner and is the result of mutations in the G6PC gene located on chromosome 17q21.
Estimated 1 in 200,000 births.

Diagnosis

Serial measurements of glucose, lactate, and ketones during a fasting study. A fasting study in GSD I will result in ketotic hypoglycemia (↑ ketone,↓ glucose) with progressive lactic acidosis (excessively high lactic acid), and failure of glucagon to treat hypoglycemia.
Liver biopsy with an assay of G6Pase activity
Gene mutation analysis for the classic type.

Treatment

Treatment consists of providing a continuous dietary(outside) source of glucose to prevent blood glucose from falling below the threshold for glucose counter-regulation.(since the body cannot produce/convert glucose from stored glycogen). Infants are given frequent feeds during the day and continuous feeds at night through a nasogastric  or gastrostomy tube. Cornstarch can be used starting at age 6 – 12 months which allows feeds to be spaced and glucose fluctuations to be minimized. Cornstarch doses and spacing of feeds should be individualized based on results of periodic metabolic evaluations and glucose monitoring. Intravenous glucose using 10% dextrose should be administered if fasting is required or if gastrointestinal illness does not allow adequate intake of carbohydrates.

Neutropenia in type Ib responds well to G-CSF therapy (Neupogen shots) and the associated inflammatory bowel disease responds to conventional therapy.

Restriction of lactose(milk sugar),galactose (content of lactose), fructose (fruit sugar), and sucrose (table sugar) is critical, as these sugars cannot be converted to glucose and will exacerbate the metabolic problems.