Prince Frederik of Luxembourg, the youngest son of Prince Robert of Luxembourg and Princess Julie of Nassau, passed away at the age of 22 on March 1 in Paris due to a rare genetic disease known as POLG. His passing came just a day after Rare Disease Day, highlighting his enduring commitment to raising awareness about the condition.

Remembering Prince Frederik: A Champion for POLG Awareness

Prince Robert announced his son’s passing on March 7 via a statement on the POLG Foundation’s website. Frederik co-founded the organization in 2022 and served as its creative director, dedicating his life to advocating for research and awareness of POLG disease.

“Frederik fought his disease valiantly until the very end,” Robert wrote. “His indomitable lust for life propelled him through the hardest of physical and mental challenges.”

Frederik is survived by his parents, his siblings Alexander and Charlotte, his cousins Charly, Louis, and Donall, his brother-in-law Mansour, his aunt and uncle Charlotte and Mark, and his beloved dog, Mushu. He was remembered as a resilient fighter and a passionate advocate. “Frederik knows that he is my Superhero,” Robert wrote. “Part of his superpower was his ability to inspire and to lead by example.”

Despite the hardships of his condition, Frederik expressed gratitude for the experiences and connections he gained through his illness. Robert shared that Frederik once told a friend, “Even though I’ll die from it … and even if my parents do not have the time to save me, I know that they will be able to save other children.”

Understanding POLG Disease

POLG disease is a severe mitochondrial disorder caused by mutations in the POLG gene, which is essential for DNA replication and repair. The disease affects multiple organs, including the brain, nerves, muscles, and liver, leading to progressive and debilitating symptoms. Robert described the condition as similar to having a faulty battery—one that never fully recharges, remains in a constant state of depletion, and eventually loses power.

Though POLG is one of the most common inherited mitochondrial diseases, affecting approximately 1 in 10,000 people, it remains classified as a rare disease. Diagnosis is challenging due to the wide range of symptoms and limited public awareness. Testing methods include molecular genetic analysis, brain imaging, and EEG testing, but even physicians can struggle to identify the disease. Frederik was diagnosed at 14, marking the beginning of his fight against the illness.

Professor Doug Turnbull, a neurology expert at Newcastle University and a member of the POLG Foundation’s scientific advisory board, described POLG deficiency as “the worst” of all mitochondrial diseases. “It is so relentlessly progressive, attacking so many different systems with sadly the same conclusion,” he stated.

The disease can impact vision, mobility, and speech, and it has a devastating prognosis. Life expectancy ranges from just three months to 12 years from the onset of symptoms.

Frederik’s Advocacy and the POLG Foundation’s Mission

For 15 years, Frederik and his mother, Julie, worked tirelessly to raise awareness of POLG disease. Together, they created a documentary sharing the perspectives of Frederik and other patients battling the condition.

The day before his passing, Frederik asked his father, “Papa, are you proud of me?” Despite struggling to speak in his final days, he sought reassurance that his life had made a difference. “We are all so very proud of you, Frederik,” Robert wrote, acknowledging his son’s incredible contributions to science and advocacy.

Advancing POLG Research: The Foundation’s Impact

Since its founding in 2022, the POLG Foundation has raised $3.6 million to fund four major research projects focused on understanding the disease’s mechanisms and potential treatments. The organization has partnered with Columbia University on Project Butterfly, a study analyzing post-mortem tissue from families affected by POLG mutations. Additionally, the foundation has developed a home-based tool to monitor functional changes in patients with mitochondrial disorders.

This year, the POLG Foundation is launching the first international POLG natural history study, which will track the progression of the disease in patients over time. Frederik himself played a crucial role in advancing POLG research—not only as a foundation leader but also as a research contributor. He provided his DNA to generate genetic sequences and pluripotent stem cells, paving the way for future scientific discoveries.

The Broader Impact of Mitochondrial Research

The implications of mitochondrial research extend beyond POLG disease. Understanding the fundamental role of mitochondria in human health can provide valuable insights into other conditions, including cancer, neurodegenerative diseases, immunologic disorders, and even aging.

Frederik’s legacy continues to drive scientific progress, offering hope for patients and families affected by mitochondrial diseases worldwide. Through the POLG Foundation’s work, his mission to improve awareness, research, and treatment options will endure, ensuring that future generations benefit from his advocacy and determination.