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.

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

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.^[4]

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.^[5]A different gene (GYS1, 138570) encodes muscle glycogen synthetase, which has normal activity in patients with glycogen-storage disease type 0.

Differential Diagnoses

Stone WL, Basit H, Adil A. Glycogen Storage Disease. StatPearls. Treasure Island (FL): StatPearls Publishing; May 29, 2023. [Full Text].
Type 0 Glycogen Storage Disease. Association for Glycogen Storage Disease. Available at https://www.agsdus.org/type-0.php. Accessed: September 21, 2023.
Spiegel R, Mahamid J, Orho-Melander M, Miron D, Horovitz Y. The variable clinical phenotype of liver glycogen synthase deficiency. J Pediatr Endocrinol Metab. Dec 2007. 20:1339-1342. [QxMD MEDLINE Link].
Orho M, Bosshard NU, Buist NR, et al. Mutations in the liver glycogen synthase gene in children with hypoglycemia due to glycogen storage disease type 0. J Clin Invest. 1998 Aug 1. 102(3):507-15. [QxMD MEDLINE Link].
Soggia AP, Correa-Giannella ML, Fortes MA, Luna AM, Pereira MA. A novel mutation in the glycogen synthase 2 gene in a child with glycogen storage disease type 0. BMC Med Genet. 2010 Jan 5. 11:3. [QxMD MEDLINE Link]. [Full Text].
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Aynsley-Green A, Williamson DH, Gitzelmann R. Asymptomatic hepatic glycogen-synthetase deficiency. Lancet. 1978 Jan 21. 1(8056):147-8. [QxMD MEDLINE Link].
Aynsley-Green A, Williamson DH, Gitzelmann R. The dietary treatment of hepatic glycogen synthetase deficiency. Helv Paediatr Acta. 1977 Jun. 32(1):71-5. [QxMD MEDLINE Link].
Aynsley-Green A, Williamson DH, Gitzelmann R, et al. Hepatic glycogen synthetase deficiency. Definition of syndrome from metabolic and enzyme studies on a 9-year-old girl. Arch Dis Child. 1977 Jul. 52(7):573-9. [QxMD MEDLINE Link].
Bachrach BE, Weinstein DA, Orho-Melander M, et al. Glycogen synthase deficiency (glycogen storage disease type 0) presenting with hyperglycemia and glucosuria: report of three new mutations. J Pediatr. 2002 Jun. 140(6):781-3. [QxMD MEDLINE Link].
Blumel P, Mullis PE. Effect of growth hormone treatment on hypoglycemia in a patient with both hepatic glycogen synthase and isolated growth hormone deficiencies. J Pediatr Endocrinol Metab. 2001 Sep-Oct. 14(8):1151-5. [QxMD MEDLINE Link].
Byrne BM, Gillmer MD, Turner RC, et al. Glucose homeostasis in adulthood and in pregnancy in a patient with hepatic glycogen synthetase deficiency. Br J Obstet Gynaecol. 1995 Nov. 102(11):931-3. [QxMD MEDLINE Link].
Chen YT, Burchell A. Glycogen storage diseases. The Metabolic and Molecular Bases of Inherited Disease. 7th ed. New York, NY: McGraw Hill; 1995. 935-65.
Laberge AM, Mitchell GA, van de Werve G. Long-term follow-up of a new case of liver glycogen synthase deficiency. Am J Med Genet A. 2003. 120(1):19-22. [QxMD MEDLINE Link].
Laberge AM, Mitchell GA, van de Werve G, Lambert M. Long-term follow-up of a new case of liver glycogen synthase deficiency. Am J Med Genet A. 2003 Jul 1. 120(1):19-22. [QxMD MEDLINE Link].
Lewis GM, Spencer-Peet J, Stewart KM. Infantile hypoglycaemia due to inherited deficiency of glycogen synthetase in liver. Arch Dis Child. 1963. 38:40-8.
Rutledge SL, Atchison J, Bosshard NU, Steinmann B. Case report: liver glycogen synthase deficiency--a cause of ketotic hypoglycemia. Pediatrics. 2001 Aug. 108(2):495-7. [QxMD MEDLINE Link].