Prince Frederik of Luxembourg, the youngest son of Prince Robert of Luxembourg and Princess Julie of Nassau, passed away in Paris on March 1 at the age of 22, a day after Rare Disease Day. He suffered from POLG, a rare genetic condition.
His father announced his death on March 7 in a statement posted on the POLG Foundation website. Frederik co-founded the foundation in 2022 and served as its creative director.
“Frederik fought his disease bravely until the very end,” Robert wrote. “His unwavering desire for life propelled him through the most difficult physical and mental challenges.”
Frederik 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. He was remembered as a resilient fighter and a strong advocate. “Frederik knows that he is my Superhero,” Robert wrote. “Part of his superpower was his ability to inspire and to lead by example.”
Robert also wrote that Frederik even expressed gratitude for having the disease. “He felt that there were so many amazing people that he would never have known had it not been for his disease,” and he 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 resulting from inherited mutations in the POLG gene, which is essential for replicating cells’ genetic material and repairing DNA. The incurable disease affects various organs, including the brain, nerves, muscles, and liver, and its symptoms can be extensive 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 said.
It is also challenging to diagnose. While it’s among the most common mitochondrial diseases, it’s still considered rare. Molecular genetic testing can detect the mutation, and brain imaging and electroencephalogram (EEG) testing can also identify associated brain changes. However, the variety of symptoms and lack of public awareness can make it difficult for physicians to diagnose. Frederik was diagnosed at age 14.
Doug Turnbull, a neurology professor 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 affect vision, mobility, and speech, and it can be fatal, with life expectancy ranging from three months to 12 years after the disease’s onset.
What does the POLG Foundation do?
In its three years of operation, the foundation has allocated $3.6 million in funding to four major research projects examining the disease’s mechanisms and potential treatments. It has also partnered with Columbia University on Project Butterfly to study post-mortem tissues from two families with the POLG mutation and launched a home-based tool to assess changes in functions and disease progression in patients with mitochondrial disorders. This year, the organization is initiating the first international POLG natural history study to gather data on how POLG disease develops in patients over time.
Frederik played a key role in advancing POLG science, not only as a foundation founder but also by providing his own DNA to generate sequences and induce pluripotent stem cells for further research.
According to Robert’s statement, mitochondrial research has implications beyond POLG. Understanding the “fundamental role of mitochondria in health and its failings in disease” can be applied to other conditions like cancer, neurodegenerative diseases, immunologic diseases, and even aging.
Frederik and his mother Julie, who worked for 15 years to raise awareness about the disease, made a video about POLG from the perspectives of Frederik and other patients.
The day before his death, Robert wrote that 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.”