Prince Frederik of Luxembourg, the youngest son of Prince Robert of Luxembourg and Princess Julie of Nassau, died in Paris at age 22 on March 1—a day after Rare Disease Day—of a rare genetic disease known as POLG.
His father announced his passing on March 7 in a statement posted on the website of the POLG Foundation, which Frederik cofounded in 2022 and was the creative director of.
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“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—who is survived by his parents; his brother, Alexander; his sister, Charlotte; his cousins, Charly, Louis, and Donall; his brother-in-law, Mansour; his aunt and uncle, Charlotte and Mark; and his dog, Mushu—was remembered as a resilient fighter and a headstrong advocate. “Frederik knows that he is my Superhero,” Robert wrote. “Part of his superpower was his ability to inspire and to lead by example.”
He even expressed gratitude for having his disease, Robert wrote. “He felt that there were so many amazing people that he would never have known had it not been for his disease,” and 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.’”
What is POLG?
POLG disease is a mitochondrial disorder caused by inherited mutations in the POLG gene—which is critical to the processes of replicating cells’ genetic material and DNA repair. The disease, which has no cure, affects multiple organs, including the brain, nerves, muscles, and liver, and symptoms can be wide-ranging and debilitating. “One might compare it to having a faulty battery that never fully recharges, is in a constant state of depletion and eventually loses power,” Robert wrote.
It’s also difficult to diagnose. While it’s one of the most common inherited mitochondrial diseases, affecting around 1 in 10,000 people, it’s considered a rare disease. Molecular genetic testing for the mutation exists, and the disease can also be detected through brain imaging to look for associated brain changes and electroencephalogram (EEG) testing, but the range in symptoms and lack of public awareness around the disease means it can be hard for even physicians to identify. Frederik was diagnosed at age 14.
Doug Turnbull, a professor of neurology 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.”
The disease can impact vision, mobility, and speech, and it can be deadly—life expectancy ranges from three months to 12 years from the onset of the disease.
What does the POLG Foundation do?
In its three year tenure, the foundation has provided $3.6 million of funding for four major research projects looking at the mechanisms of the disease and potential treatments, partnered with Columbia University on Project Butterfly to study post-mortem tissues from two families with the POLG mutation, and developed a home-based tool to assess changes in functions and disease progression of patients with mitochondrial disorders. This year, the organization is launching the first international POLG natural history study to collect data on how POLG disease develops in patients over time.
Frederik was instrumental to the advancement of the science around POLG, not only as a founder of the foundation, but also by providing his own DNA to generate sequences and induce pluripotent stem cells that can be used for further research.
The implications of mitochondrial research go beyond POLG, according to Robert’s statement. Understanding the “fundamental role of mitochondria in health and its failings in disease” can be applied to other diseases like cancer, neurodegenerative diseases, immunologic diseases, and even aging, the statement says.
Frederik and his mother Julie, who worked for 15 years to raise awareness around the disease, made a documentary about POLG from the perspective of Frederik and other patients.
The day before his death, Robert wrote, Frederik asked his father, “‘Papa, are you proud of me?’”
“He had barely been able to speak for several days, so the clarity of these words was as surprising as the weight of the moment was profound. The answer was very easy, and he had heard it oh so many times, but at this time, he needed reassurance that he had contributed all that he possibly could in his short and beautiful existence and that he could now finally move on,” Robert wrote. “We are all so very proud of you, Frederik.”