Prince Frederik and his dog, Mushu. Courtesy: polgfoundation.org

Prince Frederik of Luxembourg has died at the age of 22 from POLG mitochondrial disease, a rare genetic disorder that he was born with, his family announced.

Frederik de Nassau died in Paris on March 1, a day after internationally recognized Rare Disease Day, which takes place on the last day of February, Prince Robert of Luxembourg said in a statement posted to the POLG Foundation website. Prince Frederik founded the organization in 2021 to help raise awareness about the condition.

Prince Robert; his wife, Princess Julie of Nassau; and Prince Frederik's siblings, Alexander and Charlotte, were all able to say goodbye to him on his last day, the patriarch said. One of the last things Frederik asked him was, "Papa, are you proud of me?" according to Prince Robert.

"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," Prince Robert wrote. "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."

The young prince was remembered as a joyful person with "indomitable lust for life." He was learning Italian and was a big fan of the U.S. adaptation of "The Office," which he has seen over 10 times in its entirety, Prince Robert said.

What is POLG mitochondrial disease?
POLG is the name for a gene that provides instructions for making the active piece, called the alpha subunit, of a protein called polymerase gamma, according to the National Library of Medicine.

There are multiple POLG-related diseases and conditions, including Alpers-Huttenlocher syndrome, Ataxia neuropathy spectrum and Childhood myocerebrohepatopathy spectrum.

Frederik was born with POLG disease, but he wasn't diagnosed until he was 14 years old, his father said.

According to the POLG Foundation, the mitochondrial disorder Frederik had "robs the body's cells of energy," and can cause a variety of symptoms, including progressive dysfunction and failure of multiple organs.

"One might compare it to having a faulty battery that never fully recharges, is in a constant state of depletion and eventually loses power," the PoLG Foundation said on its website.

Experts estimate that about 2% of the population carry POLG mutations. However, the total number of people with POLG-related diseases is unclear. One study of adults in Australia with POLG mutations found that 10% of them had POLG-related diseases.

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