Researchers Deepen Understanding of Rhabdomyolysis in VLCAD

Dr. Jerry Vockley, MD, PhD, who currently works as director of the Center for Rare Disease Therapy at UPMC Children’s Hospital of Pittsburgh, was confounded. Through his research, Dr. Vockley had discovered treatments for two symptoms of very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency: heart failure and hypoglycemia. In fact, Dr. Vockley even played a role in developing triheptanoin, a recently approved VLCAD therapy. But for whatever reason, rhabdomyolysis (muscle tissue breakdown) still remained in patients.

As described by a joint news release from UPMC and the University of Pittsburgh Schools of the Health Sciences, Dr. Vockley and the research team recently gained a deeper understanding of the underlying mechanisms behind rhabdomyolysis. By finding an inflammatory link, the researchers learned more about why inflammation is happening – and how it could potentially be treated in the future. See the full findings published in Clinical & Translational Immunology. 


In an article in American Family Physician, authors describe rhabdomyolysis as:
a potentially life-threatening syndrome resulting from the breakdown of skeletal muscle fibers with leakage of muscle contents into the circulation. Multiple complications can occur and …include severe hyperkalemia that causes cardiac arrhythmia and arrest [and] acute renal failure, which occurs in approximately 15 percent of patients with the syndrome.
Dr. Vockley determined that VLCAD could cause rhabdomyolysis when exploring specific symptomatic episodes in patients. While the disease presented like inflammatory muscle disease, there were some differences, such as persistence and timing. Yet when he evaluated and tested blood samples, he noticed high levels of inflammatory markers during symptomatic episodes – and less during asymptomatic periods.
The researcher team began testing both new and stored blood samples. For example, they sourced blood from 15-year-old Bella Linz, whose rhabdomyolysis has caused over a dozen hospitalizations yearly. Although her condition is now somewhat managed using anti-inflammatory therapies, Bella wanted to contribute to a better quality of life (QOL) for other patients, which is why she joined this study.
Ultimately, researchers determined:
  • A cytokine storm, or cytokine storm syndrome, occurred during symptomatic rhabdomyolysis episodes. When this occurs, the immune system becomes overactive, releasing too many inflammatory molecules and causing the immune response to also attack healthy tissue.
  • In asymptomatic periods, patients still had higher inflammatory markers than individuals without VLCAD. However, these numbers were lower during asymptomatic periods.
  • Unlike a cytokine storm in other conditions, the inflammatory response does not occur normally in patients with VLCAD. Thus, to determine a potential treatment, researchers must learn what elements of VLCAD are triggering inflammation.

Very-Long-Chain acyl-CoA Dehydrogenase (VLCAD) Deficiency

ACADVL gene mutations cause VLCAD, a fatty acid oxidation disorder which prevents the body from breaking down certain fats or converting these fats into energy. Normally, ACADVL provides instructions to produce very-long-chain acyl-CoA dehydrogenase, an enzyme which breaks down very-long-chain fatty acids. However, patients with VLCAD have an enzyme deficiency. When the fatty acids are not broken down, it causes a host of health issues. Because VLCAD is inherited in an autosomal recessive pattern, patients must inherit one defective gene from each parent.

An estimated 1 in every 40,000 infants has VLCAD. While symptoms typically appear during infancy or early childhood, some patients may not experience symptoms until adulthood. Without treatment, VLCAD can cause brain damage or even death. But with early detection and treatment, patients may live a healthy life. Symptoms vary between patients and are often triggered by illnesses, exercise, or fasting. These include, but are not limited to:

  • Irritability
  • Excessive sleepiness
  • Poor appetite
  • Fever with no known cause
  • Nausea and vomiting
  • Low blood sugar
  • Diarrhea
  • Enlarged heart and liver
  • Muscle pain and weakness
  • Lethargy
  • Rhabdomyolysis (muscle tissue breakdown)
  • Reddish-brown urine
Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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