RICK RADER, MD ■ EDITOR-IN-CHIEF

I Prefer Mine Rare Thank You

It was lunchtime at a national medical conference, I found myself at an open table with seven other docs who welcomed the opportunity for some respite after four straight hours of death by Power Point. After the lame formalities of everyone introducing themselves and where they were from, the majority of the docs turned to their cell phones to catch up with messages from their offices, clinics, colleagues and families.

The doc sitting next to me took out a pad and scribbled notes as he repeated what was being communicated to him on the phone. They were numbers, big numbers. Very big numbers. When he got off the phone, I couldn't help but engage him. "I sure hope those weren't lab values for a patient of yours." "Not even close," he said. "I'm bidding on stamps coming up for auction, I collect stamps."

"Oh, a philatelist," I said, trying to score points and show off. He added, "My entire life, it's been my passion since I was six. After 50 years, I'm starting to play with the big boys." While I didn't ask, he was quick to add, "The first postage stamps were made available on May 1, 1840, in England, and with it began the hobby of stamp collecting." From the numbers he jotted down, Bob, the epileptologist from Omaha was placing bids on some obviously very valuable and rare stamps.

I threw in the only thing I knew about stamps, "Are you bidding on the Inverted Jenny?" One of my uncles was a stamp collector, and whenever the family got together for holidays, he would share his latest acquisitions. He told me about the Inverted Jenny. The Inverted Jenny is a United States postage stamp first issued on May 10, 1918 in which the image of the Curtiss JN-4 airplane (being used in the early days of "air mail") is printed upside-down. It is arguably the most famous error in American stamp printing. Only one sheet of 100 of the inverted stamps was ever found, making this error one of the most prized in all philately. The Curtis JN4 was also known as "Jenny," and the stamp went on sale the day before the launch of the U.S. airmail services.

"Not that there is one coming up for sale, but that stamp is out of my league. The last one sold at auction for over a million and-a-half dollars." "Wow," I replied, "guess that makes it one of the rarest stamps ever made." Bob was quick to point out that stamp collectors don't actually consider the Inverted Jennys to be particularly rare – 100 stamps is a sizeable amount within the world of philatelists. The British Guiana, one cent magenta is considered the most valuable and rarest stamp in the world. Only one of its type exists now, which is used and cut in the shape of an octagon. It sold at auction for nine-and-a-half-million dollars."

I wished Bob good luck with the upcoming auction and headed off towards the afternoon break-out sessions. I began thinking about the concept of "rare" and how it has captured the imagination of people worldwide. How "rare" does something have to be in order for it to be considered "rare"? It's not just stamps, coins, sinkholes, flowers and insects, that by their sheer numbers can be considered rare. Human traits can be rare. S. Grant writes in "10 Amazing Powers from Rare Genetic Mutations": "Compared to many other species, all humans have incredibly similar genomes.

However, even slight variations in our genes or environments can cause us to develop traits that make us unique. These differences can manifest in ordinary ways, such as through hair color, height, or facial structures, but occasionally, a person or population develops a characteristic that distinctly sets them apart from the rest of the human race." There are a multitude of "rare" characteristics that are found in our species. For instance, there is a genetic mutation where the PCSK9 gene is missing and it results in the individual being able to eat anything without getting high cholesterol. Some people have a genetic mutation that disables their copy of the CCR5 protein, which turns out, protects them from the HIV virus. People with the sickle-cell trait have a high resistance to malaria. There are "cold dwellers" who have adapted to extreme cold temperatures; they can maintain their body temperatures better without shivering and have relatively fewer sweat gland on the body and more on the face. Sherpas and other high-altitude dwellers produce fewer red blood cells and can survive in high altitudes and are less susceptible to altitude sickness. We find a tribe in Papua New Guinea, the Fore People, are immune to developing Kuru – a degenerative and fatal brain disease spread by eating other humans. There are also people with a very rare blood type known as "Rhnull"—only 40 in the world that do not have a single Rh antigen making their blood so rare that researchers refer to them as "Golden blood." Unfortunately, only nine donors of this blood exist in the world. Their blood can be life-saving to those with rare and almost unobtainable rare blood types.

Other humans such as a small group called the Moken, have crystal-clear underwater vision. There are members of the Afrikaner population (South Africans with Dutch origins) with a mutation in the SOST gene (which controls a protein, sclerostin that regulates bone growth). They have super dense bones and are immune from osteoporosis and avoid bone fractures, broken hips and hunched spines. And there are people with a rare genetic mutation of the gene DEC2 which causes them to physiologically need less sleep than the average person. They show no negative effects from sleep deprivation.

So, there are rare mutations that provide rare people with rare protective mechanisms that provide rare benefits for their lives.

But the medical world I live in is not "The only commodity in the rare disease community is the truth; truth of its recognition, existence and acceptance. But it is only the starting point." demarcated by mutations that protect people or provide people with life-enriching conditions. My field is engaged, impacted and challenged by rare genes, mutations, rare rare deletions and rare duplications that form the basis for rare diseases. I live on the outskirts of the rare disease community. I say on the outskirts because the majority of the issues I deal with daily are not rare. Autism, cerebral palsy, Down syndrome, Fragile X and intellectual disabilities are not considered "rare" by definition. They are, however, according to the legions of parents, patients, professionals, providers and pedagogues that are impacted by them daily; they are life- changing, challenging, often unchartered and lifelong.

A disease or disorder is defined as rare in the United States when it affects fewer than 200,000 Americans at any given time. In Europe they define a rare disease when it affects less than 1 in 2000.

And while the word "rare" conjures up images of a handful in Europe alone, as many as 30 million people may be affected by one of over 6000 existing rare diseases. Eighty percent of rare diseases have identified genetic origins while others are the result of infections (bacterial or viral), allergies, and environmental causes, or are degenerative and proliferative. Fifty percent of rare diseases affect children.

Clinicians may spend a lifetime without ever encountering a rare disease, or better put, "a patient with a rare disease." Dealing with a rare disease improves the clinical acumen of the provider by challenging their comfort level, causing them to think outside of the proverbial "cook book" clinical thought process. A rare disease provides the physician with the opportunity to become a sleuth and to emulate the character created by the physician author Sir Arthur Conan Doyle, the legendary detective Sherlock Holmes. Holmes provides the foundation for working with the rare disease universe, "Once you eliminate the impossible, whatever remains, no matter how improbable, must be truth."

The only commodity in the rare disease community is the truth; truth of its recognition, existence and acceptance. But it is only the starting point.

Rare Disease Day takes place on the last day of February each year. The main objective of Rare Disease Day is to raise awareness among the general public and decision-makers about rare diseases and their impact on patients' lives. Some of the concerns related to rare diseases is the lack of scientific knowledge and quality information on the disease which often results in a delay in diagnosis and access to appropriate treatment and care. Unfortunately, we are also all too familiar with those aspects of the rare disease and disabilities community which are not rare; inequality, indifference, ignorance and injustice.

For decades, Exceptional Parent magazine (EP) has served as a bastion of information, resources, advocacy and support for the rare disease community. We have long nodded in agreement with the old medical school axiom: "When you hear hoof beats, think of horses, but don't overlook the possibility that they may be coming from zebras."•

ANCORA IMPARO In his 87th year, the artist Michelangelo (1475 -1564) is believed to have said "Ancora imparo" (I am still learning). Hence, the name for my monthly observations and comments. — Rick Rader, MD, Editor-in-Chief, EP Magazine Director, Morton J. Kent Habilitation Center Orange Grove Center, Chattanooga, TN