Glycogen-Storage Disease Type 0 (GSD-0) (Glycogen Synthetase Deficiency) Clinical Presentation

Updated: May 03, 2017
  • Author: Reem Saadeh-Haddad, MD; Chief Editor: Luis O Rohena, MD, MS, FAAP, FACMG  more...
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Presentation

History

The most common clinical history in patients with glycogen-storage disease type 0 (GSD-0) is that of an infant or child with symptomatic hypoglycemia or seizures that occur before breakfast or after an inadvertent fast. In affected infants, this event typically begins after they outgrow their nighttime feeds. In children, this event may occur during acute GI illness or periods of poor enteral intake.

Mild hypoglycemic episodes may be clinically unrecognized, or they may cause symptoms such as drowsiness, sweating, lack of attention, or pallor. Uncoordinated eye movements, disorientation, seizures, and coma may accompany severe episodes.

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Physical

Glycogen-storage disease type 0 affects only the liver. Growth delay may be evident with height and weight percentiles below average. Abdominal examination findings may be normal or reveal only mild hepatomegaly, if any. Other glycogen storage disorders present with significant hepatomegaly.

Signs of acute hypoglycemia may be present, including the following:

  • Lethargy

  • Apathy

  • Jitteriness

  • Diaphoresis

  • Tachycardia

  • Pallor

  • Nausea and vomiting

  • Headache

  • Mental confusion

  • Visual disturbances

  • Dysarthria

  • Hypotonia

  • Ataxia

  • Seizures

  • Coma

  • Death

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Causes

Glycogen-storage disease type 0 is caused by genetic defects in the gene that codes for liver glycogen synthetase (GYS2), which is located on chromosome band 12p12.2. [2]

Glycogen synthetase catalyzes the rate-limiting reaction for glycogen synthesis in the liver by transferring glucose units from uridine 5'-diphosphate (UDP)-glucose to a glycogen primer. Its action is highly regulated by a mechanism of phosphorylation and dephosphorylation and modulated by counter-regulatory hormones including insulin, epinephrine, and glucagon.

Mutations in the gene for liver glycogen synthetase (GYS2, 138571) result in decreased or absent activity of liver glycogen synthetase and moderately decreased amounts of structurally normal glycogen in the liver. Mutational studies of patients with glycogen-storage disease type 0 do not demonstrate correlations between genotype and phenotype. [3] A different gene (GYS1, 138570) encodes muscle glycogen synthetase, which has normal activity in patients with glycogen-storage disease type 0.

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