Glycogen-branching enzyme deficiency

Glycogen-branching enzyme deficiency (GBED) is a rare, autosomal recessive metabolic disorder that affects the way the body stores glucose. It is one of the many types of glycogen storage diseases (GSDs), specifically classified as GSD type IV (GSD IV), also known as Andersen's disease. This condition is caused by mutations in the GBE1 gene, which encodes the glycogen-branching enzyme necessary for the proper formation of glycogen. Without sufficient activity of this enzyme, an abnormal form of glycogen, called polyglucosan, is produced and accumulates in various tissues, leading to their dysfunction.

Symptoms and Signs

The clinical presentation of GBED can vary widely among affected individuals. Symptoms typically manifest in infancy or early childhood and may include muscle weakness, hypotonia (reduced muscle tone), Failure to thrive, and progressive liver enlargement leading to Liver failure. In severe cases, affected infants may present with Cardiomyopathy, which can be fatal. Neurological involvement can lead to developmental delays and, in some cases, Seizures.

Diagnosis

Diagnosis of GBED is based on clinical presentation, biochemical tests showing abnormal glycogen structure, and confirmed by genetic testing identifying mutations in the GBE1 gene. Enzyme activity assays in affected tissues (such as liver or muscle) can also support the diagnosis. Prenatal diagnosis is available for families with a known mutation.

Treatment

There is no cure for GBED, and treatment is supportive and symptomatic. Management strategies may include nutritional support to manage Hypoglycemia (low blood sugar levels), physical therapy to address muscle weakness, and medications to control seizures if present. Liver transplantation may be considered in cases of severe liver failure. Due to the risk of cardiomyopathy, regular cardiac monitoring is recommended.

Prognosis

The prognosis for individuals with GBED varies depending on the severity of symptoms and the onset of complications. Early-onset forms of the disease, particularly those presenting with cardiomyopathy, tend to have a poorer prognosis, with many affected infants not surviving beyond the first year of life. For those with milder forms, lifespan may be normal, though they may experience chronic health issues related to their condition.

Epidemiology

GBED is a very rare condition, though its exact prevalence is unknown. It has been reported in various ethnic groups worldwide.

See Also

• Glycogen storage disease
• Metabolic disorder
• Liver transplantation
• Cardiomyopathy