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Glycogen storage disease due to liver glycogen phosphorylase deficiency
A rare form of glycogen storage disease (GSD) characterized by a deficiency of hepatic glycogen phosphorylase leading to impaired glycogenolysis, and characterized by hepatomegaly and growth delay in childhood.
ORPHA:369
Classification level: Disorder
- GSD due to liver glycogen phosphorylase deficiency
- Glycogen storage disease type 6
- Glycogenosis due to liver glycogen phosphorylase deficiency
- GSD type 6
- Hepatic glycogen phosphorylase deficiency
- Hepatic phosphorylase deficiency
- Hers disease
- Liver glycogen phosphorylase deficiency
- Glycogenosis type 6
- GSD type VI
- Glycogen storage disease type VI
- Glycogenosis type VI
Prevalence: Unknown
Inheritance: Autosomal recessive
Age of onset: Childhood
Glycogen storage disease due to liver glycogen phosphorylase deficiency (GSD-VI) affects approximately 1/65,000-85,000 live births but is probably underdiagnosed. Memmonite populations are at increased risk for the disease, with a prevalence of 1/1,000.
The disease usually occurs in childhood and is characterized by hepatomegaly and growth delay. Hypoglycemic episodes are mild or absent, and hypertransaminasemia and hyperlipidemia are moderate and inconstant. Hepatomegaly is usually shrinking with age and disappears at puberty.
Transmission is autosomal recessive and mutations in the PYGL gene (14q21-q22) have been identified in patients.
Measuring glycogen phosphorylase activity can be helpful for a definitive diagnosis (blood cells or liver tissue), however, phosphorylase activity can be normal in the blood cells of patients with GSD-VI. Non-invasive diagnostic confirmation is made by molecular analysis of PYGL gene. Liver biopsy is no longer necessary for the diagnosis, and is reserved when genetic analysis is inconclusive.
Other forms of GSDs associated with hepatomegaly and hypoglycemia (especially GSD-I, GSD-III and GSD-IX), and disorders of fructose metabolism should also be considered. It is not possible to distinguish between GSD-VI and GSD-IX based only on clinical or laboratory data; enzymatic assays and molecular testing are necessary.
Antenatal and preimplantation genetic testing are technically possible provided pathogenic variants have previously been identified in the proband. However, there are no demands for such procedures, owing to the benignity of this type of GSD.
Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them that there is a 25% risk of having an affected child at each pregnancy.
A diet with high carbohydrates intake and regular meals prevents hypoglycemia in children, but most patients require no specific treatment.
Prognosis is usually good.
Last update: August 2024 - Expert reviewer(s): Dr Roseline FROISSART - Pr Philippe LABRUNE | MetabERN*
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