Genetics of von Gierke Disease (Glycogen-Storage Disease Type 1) Clinical Presentation

Updated: Aug 10, 2017
  • Author: Karl S Roth, MD; Chief Editor: Maria Descartes, MD  more...
  • Print
Presentation

History

Initial symptoms of neonatal hypoglycemia occur shortly after birth in patients with glycogen-storage disease type I (GSD I), and patients do not respond to glucagon administration. Symptoms include the following:

  • Tremors

  • Irritability

  • Cyanosis

  • Seizures

  • Apnea

  • Coma

Older infants may present with the following:

  • Frequent lethargy

  • Difficult arousal from overnight sleep

  • Tremors

  • Overwhelming hunger

  • Poor growth

  • Apparent increase in abdominal girth, although extremities appear thin

  • A doll-like facial appearance caused by adipose tissue deposition in the cheeks

Young children with glycogen-storage disease type Ia may experience nosebleeds.

Young children with glycogen-storage disease Ib may have frequent otitides, gingivitis, and boils.

Symptoms of severe hypoglycemia in patients of all ages are likely to follow any illness that causes mild anorexia or fasting (eg, viral gastroenteritis).

In middle childhood, patients may manifest evidence of rickets and anemia.

Patients with glycogen-storage disease Ib at all ages may be affected by a Crohnlike ileocolitis (pseudocolitis). The severity of the primary disorder is not correlated with the intestinal symptoms.

Next:

Physical

Affected infants are healthy at birth, although some are born with an enlarged liver.

  • Careful abdominal examination is mandatory for any neonate with hypoglycemia.

  • Abdominal protuberance develops early because of massive hepatomegaly.

  • Splenomegaly does not occur.

  • The liver is firm and uniform in consistency in early life but may become nodular with the development of adenoma.

The patient may present with poor growth, short stature, and rachitic changes.

Gingivitis and compromised dentition may be present.

Xanthoma may be found on extensor surfaces, such as the elbows and knees.

Ultrasonography may reveal large kidneys in patients of all ages. Proteinuria may accompany this finding.

In addition to hypoglycemia, an increased plasma lactate value is a characteristic laboratory finding in a symptomatic newborn with glycogen-storage disease I. The increased lactate originates from the flooding of the glycolytic pathway by glucose-6-phosphate, which is derived from breakdown of glycogen, cannot be cleaved to free glucose, and is released into blood.

Previous
Next:

Causes

Glycogen-storage disease Ia and Ib are autosomal recessive genetic traits caused by mutations at loci 17q21 and 11q23, respectively.

Glycogen-storage disease Ia is caused by deficient activity of the enzyme glucose-6-phosphatase, representing at least 14 distinct allelic variants.

Glycogen-storage disease Ib is caused by deficiency of glucose-6-phosphate translocase, which is responsible for importing glucose-6-phosphate from the cytosol to the interior of the microsome, thus bringing substrate into contact with enzyme. To date, allelic variation in this disorder has not been explored.

A particular molecular pattern has been suggested in hepatocytes, which are transformed into adenomata. [9]

Previous