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Glycogen storage disease due to hepatic glycogen synthase deficiency
A genetically inherited anomaly of glycogen metabolism and a form of glycogen storage disease (GSD) characterized by fasting hypoglycemia. This is not a glycogenosis, strictly speaking, as the enzyme deficiency decreases glycogen reserves.
ORPHA:2089Classification level: Disorder
- GSD due to hepatic glycogen synthase deficiency
- GSD type 0a
- Glycogen storage disease due to liver glycogen synthase deficiency
- Glycogen storage disease type 0a
- Glycogenosis type 0a
- Prevalence: <1 / 1 000 000
- Inheritance: Autosomal recessive
- Age of onset: Childhood
- ICD-10: E74.0
- OMIM: 240600
- UMLS: C1855861
- MeSH: -
- GARD: 2513
- MedDRA: -
It is an extremely rare disease; about 20 cases have been reported in the literature so far.
It commonly appears in infancy or in early childhood. Patients present with morning fatigue and fasting hypoglycemia (without hepatomegaly) associated with hyperketonemia but without hyperalaninemia or hyperlactacidemia. After meals, major hyperglycemia associated with lactate and alanine increase and hyperlipidemia is observed.
Glycogen synthetase deficiency is caused by mutations in the GYS2 gene (12p12.2).
Biological results after glucose loading test strongly suggest the diagnosis, but formal diagnosis requires a liver biopsy showing a slightly decreased glycogen concentration and evidence of the enzyme deficiency (it is not expressed in muscles, erythrocytes, leukocytes, or fibroblasts). Molecular analysis revealing a mutation in the GYS2 gene confirms the diagnosis. Mutation analysis is an alternative to liver biopsy.
Differential diagnoses include fructose intolerance, GSD type 1 (see these terms), and hypoglycemia.
Transmission is autosomal recessive.
Management and treatment
The condition is treated with a specific diet that includes frequent meals with high protein intake during the day and addition of uncooked starch in the evening.
Prognosis is favorable when the disease is correctly managed.
Article for general public
- Emergency guidelines
- English (2012, pdf)