Decoding Glycogen Storage Disease IV: Understanding, Diagnosing, and Genetic Testing for Classic Hepatic Type

Expert Reviewed By: ⁠Dr. Brandon Colby MD

Understanding Glycogen Storage Disease IV

Glycogen Storage Disease IV (GSD IV), also known as Andersen Disease or Glycogen Branching Enzyme Deficiency, is a rare autosomal recessive genetic disorder. It is caused by mutations in the GBE1 gene, which encodes the glycogen branching enzyme responsible for the proper formation of glycogen. This enzyme deficiency leads to the accumulation of abnormal glycogen molecules in various tissues, primarily affecting the liver. GSD IV has a wide range of clinical manifestations, with different subtypes, ages of onset, severity, and clinical features (Synonyms: Andersen Disease, GSD IV, Glycogen Branching Enzyme Deficiency, Glycogen Storage Disease IV, Glycogenosis IV).

Diagnosing Glycogen Storage Disease IV

Diagnosing GSD IV can be challenging due to its variable clinical presentations and overlapping symptoms with other hepatic glycogen storage diseases. A combination of clinical, biochemical, and molecular genetic testing is typically used to establish a diagnosis. Histopathological examination of liver tissue samples can reveal the presence of abnormal glycogen, while enzyme assays can measure the activity of the glycogen branching enzyme (A Broad Characterization of Glycogen Storage Disease IV Patients: A Clinical, Genetic, and Histopathological Study).

Massively parallel sequencing, including targeted gene sequencing and exome sequencing, has emerged as a valuable diagnostic tool for GSDs with liver involvement. These methods allow for the simultaneous analysis of multiple genes, providing a more accurate and efficient diagnosis (Diagnosis of hepatic glycogen storage disease patients with overlapping clinical symptoms by massively parallel sequencing: a systematic review of literature).

Genetic Testing for Glycogen Storage Disease IV

Genetic testing plays a crucial role in the diagnosis, management, and treatment of GSD IV. It can help confirm the diagnosis, identify the specific GBE1 gene mutation, and determine the subtype of the disease. Genetic testing can also be used for carrier testing, prenatal diagnosis, and preimplantation genetic diagnosis for at-risk families.

Confirming the Diagnosis

Identifying the specific GBE1 gene mutation can confirm the diagnosis of GSD IV. This information can also provide insight into the severity and prognosis of the disease, as different mutations can result in varying clinical manifestations (A Broad Characterization of Glycogen Storage Disease IV Patients: A Clinical, Genetic, and Histopathological Study).

Carrier Testing and Prenatal Diagnosis

Carrier testing can be performed for individuals with a family history of GSD IV or those in high-risk populations. This testing can help identify couples at risk of having a child with GSD IV. Prenatal diagnosis can then be offered to pregnant women who are carriers of the GBE1 gene mutation, allowing for informed decision-making and early intervention if needed.

Preimplantation Genetic Diagnosis

For couples at risk of having a child with GSD IV, preimplantation genetic diagnosis (PGD) can be an option. PGD involves testing embryos created through in vitro fertilization (IVF) for the presence of the GBE1 gene mutation before implantation. This allows for the selection of embryos without the mutation, reducing the risk of having a child with GSD IV.

Treatment and Management of Glycogen Storage Disease IV

There is currently no cure for GSD IV, and treatment focuses on managing symptoms and complications. Nutritional therapy, including a high-protein diet, can help support liver function and prevent muscle wasting. Liver transplantation has been shown to improve the quantity and quality of life for GSD IV patients with severe liver involvement; however, it may not alter the extrahepatic progression of the disease (Liver Transplantation for Glycogen Storage Disease Type IV).

Early diagnosis and intervention are crucial for managing GSD IV and preventing complications. Genetic testing plays a vital role in the diagnostic process, as well as guiding treatment decisions and family planning for those affected by this rare genetic disorder.

About The Expert Reviewer

Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of  and the author of ⁠⁠Outsmart Your Genes.

Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (⁠⁠ACMG), an Associate of the American College of Preventive Medicine (⁠⁠ACPM), and a member of the National Society of Genetic Counselors (⁠NSGC)