GSD type IV

Glycogen Storage Disease Type IV (GSD IV), also known as Andersen's Disease, is a rare genetic disorder characterized by the accumulation of an abnormal form of glycogen, known as polyglucosan, in the body's cells. This condition is caused by a deficiency of the enzyme glycogen branching enzyme (GBE), which is crucial for the proper formation of glycogen. The abnormal glycogen interferes with the normal functioning of various organs, including the liver, muscles, and nervous system.

Causes

GSD IV is caused by mutations in the GBE1 gene, which provides instructions for making the enzyme necessary for glycogen synthesis. These mutations lead to the production of a defective enzyme, resulting in the accumulation of poorly branched glycogen molecules. GSD IV is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected by the disorder.

Symptoms

The symptoms of GSD IV can vary widely among affected individuals, ranging from mild to severe. The most common form of the disease, the progressive liver form, typically presents in infancy or early childhood with symptoms such as failure to thrive, muscle weakness, and liver enlargement. Without treatment, this form can lead to liver failure and death in early childhood. Other forms of GSD IV include the non-progressive liver form, the neuromuscular form, and the adult polyglucosan body disease form, each associated with different sets of symptoms and outcomes.

Diagnosis

The diagnosis of GSD IV is typically based on a combination of clinical evaluation, laboratory testing, and genetic testing. Laboratory tests may reveal elevated liver enzymes, indicating liver damage, and a liver biopsy can confirm the presence of abnormal glycogen. Genetic testing can identify mutations in the GBE1 gene, confirming the diagnosis.

Treatment

There is currently no cure for GSD IV, and treatment is primarily supportive and symptomatic. Management of the progressive liver form may include nutritional support and measures to prevent liver failure. In severe cases, a liver transplant may be necessary. For individuals with the neuromuscular form of GSD IV, physical therapy and other interventions may help manage muscle weakness and maintain mobility.

Prognosis

The prognosis for individuals with GSD IV varies depending on the form of the disease and the severity of symptoms. Those with the progressive liver form typically have a poor prognosis without a liver transplant, while individuals with other forms of the disease may have a more variable outlook.