Demystifying McArdle Disease: A Guide to Understanding, Diagnosing, and Genetic Testing

Expert Reviewed By: ⁠Dr. Brandon Colby MD

McArdle disease, also known as glycogen storage disease type V (GSD-V), is a rare genetic disorder affecting the body’s ability to break down glycogen in muscles. This leads to various symptoms, including muscle weakness, fatigue, and exercise intolerance. In some cases, it can even result in life-threatening complications like acute kidney injury. In this article, we will explore the complexities of McArdle disease, its diagnosis, and the role of genetic testing in managing this condition.

Understanding McArdle Disease

McArdle disease is caused by a deficiency in the enzyme myophosphorylase, which is responsible for breaking down glycogen in muscles. This deficiency leads to the accumulation of glycogen in muscle cells, causing muscle dysfunction and a range of symptoms. The severity of the disease can vary from mild to severe, with some individuals experiencing only mild exercise intolerance, while others may suffer from recurrent episodes of muscle breakdown (rhabdomyolysis) and kidney damage.

Some case reports have highlighted the diverse presentations of McArdle disease, such as a young woman requiring temporary hemodialysis due to acute kidney injury, a 19-year-old male with recurrent rhabdomyolysis, and a 20-year-old patient with both anorexia nervosa and McArdle disease. These cases highlight the importance of considering metabolic myopathies like McArdle disease in patients presenting with muscle dysfunction and kidney injury.

Diagnosing McArdle Disease

Diagnosing McArdle disease can be challenging due to its variable presentation and rarity. A combination of clinical evaluation, laboratory tests, imaging studies, and genetic testing is often required to establish a definitive diagnosis. Muscle biopsy, once considered the gold standard for diagnosis, is now being replaced by less invasive methods like genetic testing.

Some potential muscle biomarkers have been identified in a recent study on the muscle proteome of McArdle disease patients, which could potentially aid in the diagnosis and monitoring of the disease. These biomarkers include proteins involved in muscle contraction and calcium homeostasis, which are crucial for muscle function.

The Role of Genetic Testing in McArdle Disease

Confirming the Diagnosis

Genetic testing plays a crucial role in the diagnosis of McArdle disease, as it can confirm the presence of mutations in the PYGM gene responsible for the deficiency of myophosphorylase enzyme. This non-invasive method can be performed using a blood sample and is particularly helpful when other diagnostic tests are inconclusive or when a muscle biopsy is not feasible.

Carrier Testing and Family Planning

Since McArdle disease is an autosomal recessive disorder, both parents must carry a mutated copy of the PYGM gene for their child to be affected. Genetic testing can help identify carriers of the mutated gene, allowing couples to make informed decisions about family planning and assess the risk of having a child with McArdle disease.

Prenatal and Preimplantation Genetic Testing

For couples at high risk of having a child with McArdle disease, prenatal genetic testing can be performed during pregnancy to determine if the fetus is affected. Additionally, preimplantation genetic testing can be done during in vitro fertilization (IVF) to screen embryos for the presence of the PYGM gene mutation, allowing only unaffected embryos to be implanted.

Guiding Treatment and Management

Genetic testing can also help guide the treatment and management of McArdle disease by providing information on the specific mutation and its potential impact on disease severity. This information can be valuable in tailoring treatment plans, monitoring disease progression, and identifying potential complications.

In conclusion, understanding and diagnosing McArdle disease is essential for effective management and prevention of complications. Genetic testing plays a pivotal role in this process, offering valuable insights into the disease and guiding personalized treatment strategies. As research continues to uncover more about this rare disorder, genetic testing will remain a vital tool in the fight against McArdle disease.

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)