Glycogen storage disease due to glycogen branching enzyme deficiency

Glycogen storage disease due to glycogen branching enzyme deficiency, also known as glycogen storage disease type IV (GSD IV) or Andersen disease, is a rare inherited metabolic disorder caused by mutations in the GBE1 gene, which encodes the glycogen branching enzyme (1,4-alpha-glucan-branching enzyme). This enzyme is essential for creating the normal branched structure of glycogen. When it is deficient, an abnormal, poorly branched glycogen (resembling amylopectin) accumulates in various tissues, particularly the liver, skeletal muscle, heart, and nervous system, leading to progressive organ damage. The clinical presentation of GSD IV is highly variable, ranging from a severe perinatal/neonatal form (sometimes presenting as fetal akinesia deformation sequence or hydrops fetalis) to a classic hepatic form that typically manifests in infancy with hepatosplenomegaly, failure to thrive, and progressive liver cirrhosis that can lead to liver failure and death in early childhood. Neuromuscular forms also exist, including a childhood-onset form with myopathy and cardiomyopathy, and an adult-onset form known as adult polyglucosan body disease (APBD), which presents with progressive upper and lower motor neuron dysfunction, peripheral neuropathy, neurogenic bladder, and cognitive decline. There is currently no specific enzyme replacement therapy or definitive cure for GSD IV. Treatment is primarily supportive and depends on the subtype. Liver transplantation has been performed successfully in children with the progressive hepatic form and can be life-saving, though abnormal glycogen may still accumulate in other tissues post-transplant. For neuromuscular forms, management focuses on physical therapy, supportive care, and symptom management. Dietary management and monitoring of cardiac and hepatic function are important components of ongoing care. Genetic counseling is recommended for affected families.

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