The Loneliest Fight
A person with a rare disease is doubly isolated: He or she lives with serious illness as well as uncertainty about treatment options. There is no choice for a patient but to become an expert and advocate extraordinaire.
By Kristin Ohlson published September 3, 2012 - last reviewed on October 27, 2020
One morning, when Laura Rossano was a kid, she woke up with her left arm folded against her chest. To her horror, she couldn't straighten it—she still can't, 11 years later. Likewise, her hips are frozen in one position, and her right arm is forever rigid against her side. Rossano has a rare genetic condition in which her muscles can turn to bone while she sleeps. "Nighttime is my enemy," she says.
Although she was diagnosed at age 5 with fibrodysplasia ossificans progressiva, the disease didn't become aggressive until she was in middle school—the worst possible time to be different from your peers. "In 90 days I lost all my independence," the 23-year-old recalls of her painful launch into puberty. When she arrived for eighth grade in a wheelchair, her friends dropped her, their parents stopped socializing with her parents, and the officials at her parochial school grumbled about needing to make the school handicapped-accessible. She became severely depressed.
Any serious illness or even temporary disability can make one feel isolated and manhandled by fate, but for people with rare diseases—defined as ones afflicting 200,000 people or fewer in the U.S.—there are often additional challenges. For the most part, these patients go from doctor to doctor seeking a diagnosis. When or if they get one, there is often no treatment and no physician knowledgeable about their rare disease. The impact is like being rocketed off to a distant planet. Usually they've never heard of their condition until they are diagnosed. And usually they are young—many of these often-fatal diseases are genetic.
There are around 7,000 rare illnesses, and some 50 new ones are recorded every year—thanks to better identification of disease subsets, such as newly defined lymphomas or leukemias. Most cancers, in fact, are rare disorders. And even though the constituency for each illness is small, together they affect up to 8 percent of the population—more than 25 million Americans, the same number as those struggling with diabetes. This high number may be due in part to awareness, with more patients and families willing to discuss rare diseases in the media. Also, the Internet has made advocacy much easier.
As most physicians aren't familiar with these diseases, seeking a diagnosis can be terribly frustrating. The challenge for a doctor to be able to recognize every rare disease is made even more difficult because symptoms may appear only gradually or one at a time. Fifteen percent of people who suffer from rare illnesses report that it took them more than five years to get a diagnosis. And even then, patients often find that there are few treatments and even fewer knowledgeable professionals.
Inadequate resources mean such illnesses are cast aside as "orphans." Because of the small number of individuals afflicted, "it's difficult to make the case for funding," says Glenn Gaulton, chief science officer at the University of Pennsylvania's Perelman School of Medicine. But since funding could mean finding a cure, more and more patients and their families are becoming their own advocates.
Here, in addition to Rossano's story, are the journeys of three individuals who are similarly affected by rare conditions. They not only cope with the daily challenges of their illness but also manage to flourish, even as they fight for an as-yet- unknown cure.
- UREA CYCLE DISORDER: An enzyme deficiency caused by a genetic mutation leads to a toxic buildup of ammonia in the blood.
- PREVALENCE: UCDs, as a group, occur in one in 30,000 live births.
For Eva Oseland, every day is an almost perfect replica of the one before, but she doesn't balk at the rigors of her schedule. It helps keep her 10-year-old grandson Matthew healthy and out of the hospital. Matthew was diagnosed in utero with a urea cycle disorder caused by an enzyme deficiency leading to a toxic buildup of ammonia in the blood.
Sadly, Oseland was already seasoned at managing this disease, which is caused by a rare hereditary mutation. Her own son Tyler had been born with the same condition seven years earlier. After he began vomiting and had trouble breathing, he was flown to the Loma Linda University Medical Center in southern California. There, a doctor acted on a hunch and tested Tyler's blood for ammonia. "His blood ammonia level was 1,600," Oseland recalls. "Normal can be as low as zero."
Tyler survived the crisis, but was given a 20 percent chance of living a month. There was no real treatment for the disorder and only a few experts worldwide. In fact, there was no record of any babies with the condition surviving to their first birthday. Oseland enrolled Tyler in a clinical trial; data from that trial led to the most commonly used treatment to date. With her sister, she tracked every detail of Tyler's life. They recorded, for example, how many times he urinated during the day and how many times he refused to eat. "The doctor thought we were silly at first," she says, but in the end the discipline informed Oseland and her sister.
They noted that Tyler's ammonia levels rose with each new tooth. To manage the stress of teething, his body would break down its own protein muscle mass for energy. Oseland found that giving him extra calories during times of stress could stave off ammonia buildup and a trip to the hospital.
Remarkably, Tyler lived to the age of 7, though his short life was punctuated with some 300 visits to the hospital. Just months after he died, Oseland's daughter gave birth to Matthew, who had the same condition. Since Oseland knew how to manage the disease—and because survival depends on a careful routine that avoids germs and balances stress with calories—her daughter agreed that Oseland should raise him. Matthew has gone to the hospital only twice; it helps that he is home-schooled and kept away from others to prevent contamination. Though he's socially isolated, Oseland says that he is a bright and active child.
- MULTICENTRIC CASTLEMAN'S DISEASE: The immune system produces excess inflammatory cells that attack vital organs in this lymphoma-like condition.
- PREVALENCE: Estimated at fewer than one in 100,000
The fatigue and abdominal pain started when David Fajgenbaum was a third-year medical student at the University of Pennsylvania in 2010, but he didn't seek medical attention right away. He diagnosed himself as having gall bladder trouble, something he could wait out as he prepared for his OB/GYN final. After his exam, feverish and dripping with sweat, he went to the hospital. There, he found out that his liver, kidneys, and bone marrow were all failing.
No one knew what was going on. He was immediately placed in intensive care, and after seven weeks there on high-dose steroids, he seemed to get better. A second attack four weeks later almost killed him. "I called in my priest for last rites and said goodbye to my family," Fajgenbaum says.
One of his doctors finally made a diagnosis: multicentric Castleman's disease, a rare lymphoma-like condition in which the immune system produces excess inflammatory cells that attack the vital organs. His doctor blasted him with chemo, hoping to kill off the antibodies before they killed him. "My doctor was talking about my survival in terms of hours, not days and weeks," Fajgenbaum says. But he improved and was released from the hospital.
Frits van Rhee, a specialist who focuses on Castleman's at the University of Arkansas, says that Fajgenbaum has the most aggressive case he's ever seen and pledged to help him make it past his 25th birthday and, he hopes, all the way to his 75th. He put Fajgenbaum on a drug originally developed to treat multiple myeloma. It kept him healthy enough to work through his fourth year of medical school, but a recent recurrence sent him back to the hospital. He has since rallied, with the help of van Rhee.
The experience of having a disease that afflicts only about 200 Americans each year brought back the feelings of isolation Fajgenbaum had had two years earlier, when his mother died of brain cancer. "I felt so alone," he says. "A huge number of people in college have ailing parents, but it's not normal to talk about grief in the cafeteria or at a party."
His response was to form National Students of AMF (Actively Moving Forward), an organization that now has 43 official campus chapters and has helped thousands of students navigate the grief that accompanies the loss of a loved one. "I put hundreds of hours into building AMF, and that supported my own grief," Fajgenbaum says. "You get so much benefit from giving back; that's how I coped."
He's coping in a similar way now by trying to help others with rare diseases, working as a strategic planning adviser to the Center for Orphan Disease Research and Therapy at Penn. Between AMF, medical school, and his work on behalf of other rare-disease patients, there is no concept of downtime. "When I got sick, all that I had control over was taken from me," Fajgenbaum says. "Thanks to a miracle, I recovered. This is overtime, and every second counts."
- CHORDOMA: Remnants of the notochord, the embryonic precursor of the spinal chord, generate brain and spinal tumors.
- PREVALENCE: One in 1 million
In 2006, Josh Sommer was just about to go rock climbing with his friends at Duke University when his mother called. She told him that she was in town and wanted to see him. When she pulled up outside his dorm, his dog jumped out of the car and ran towards him. "I knew something was wrong or else she wouldn't have brought my dog," he says. "Then we sat on my bed and we talked; it was one of the most surreal moments of my life."
Earlier, he had suffered two weeks of intense headaches, and his physician mother finally motivated him to get tested. An MRI revealed a cancerous tumor in his brain; and not just any cancer but chordoma. It results when remnants of the notochord, which forms the spine in utero, remain behind, generating brain and spine tumors.
Even though chordoma is often found in the brain, it's actually a bone tumor. "Chordoma is as different from brain cancer as it is from breast cancer," he says. "When I was diagnosed, there was a real paucity of research, with only one person in the country who had a federal grant to work on it."
Sommer had the tumor surgically removed, but because it can grow back, he undergoes a brain scan every six months. There aren't any drugs that treat chordoma, so he set out to transform the landscape for research. He dropped out of college and founded the Chordoma Foundation.
In only six years, the foundation has become an indispensable resource for researchers worldwide. Previously, studies were hampered by a lack of high-quality chordoma cell lines, which are tumor cells that reproduce infinitely. The foundation is now the sole source of chordoma cell lines, made freely available for research. The foundation has also created a bio-bank of tumor tissue and an animal model repository, also critical for research. And it funds studies, including work that has led to the identification of genetic markers inside chordoma tumors, which may provide clues for drug development.
Sommer's work has brought him friendships with many chordoma patients, as well as with those who have founded organizations to fight other rare illnesses. They're the ones who understand the terror of having an orphan disease and the exhilaration of being part of the solution. "It seems we hit a new milestone every week," Sommer says. "There are a lot of people depending on me, and there's nothing else I could do that's as stimulating and fulfilling."
- FIBRODYSPLASIA OSSIFICANS PROGRESSIVA: A genetic disease, it prompts the body's muscles to turn to bone, causing paralysis.
- PREVALENCE: One in 2 million
One day, when she was in kindergarten, Laura Rossano's neck and back became so swollen that her mother had to cut off her clothes. The swelling subsided, but her neck and shoulders remained stiff. Her parents took her to one doctor after another to find out what was happening.
Finally, an orthopedic surgeon ordered X-rays. Rossano and her parents watched as he pointed to the images and announced that she had fibrodysplasia ossificans progressiva, a rare genetic condition in which the body's muscles gradually turn to bone. "One day bone will form around her ribs, and she will stop breathing and die," he announced. "He left no room for me to hope," Rossano, now 23, says.
Fortunately, the disease lay dormant for years. "I couldn't fix my hair because I had limited mobility in my neck and arms, but from the hips down I was fine," Rossano says. Everything changed when she hit puberty and had the life-altering experience of waking up nearly paralyzed. Suddenly, she was in a wheelchair, requiring help with everything. It was a dark time, and she had only her family for encouragement.
High school proved much easier than middle school. A stellar student, she found new friends who were more empathetic. Being determined helped. Not only did she manage her disease, but at graduation she even walked, with her brother's steady arm for support, to receive her diploma—a feat that took months of practice. At Hofstra University, she had friends who were compassionate enough to make sure they met up at handicapped-accessible restaurants. She graduated from college with honors.
Up until her senior year, she had hoped to become a poetry teacher. But her longtime doctor, a specialist in fibrodysplasia, repeatedly asked her to address medical students about her condition, and she finally agreed. Standing in front of the students, she suddenly felt she was owning up to who she was. "It was a turning point to speak to them," she says.
Rossano is now getting a master's degree at Hofstra in rehabilitation counseling; she plans to work with young people like herself. "Many people with disabilities don't know they can make it through high school, let alone college," she says. She wants to show them that there is hope in their journey.
Collaborate and Conquer
In the world of rare diseases, the last decade has seen real progress. The Office of Rare Diseases Research at the National Institutes of Health has had its budget double in the past 10 years and is now working on many fronts, including gathering a database of people with these illnesses. "One problem is locating the patients," director Stephen Groft says. "A registry would lead to natural history studies, allowing us to monitor patients over their lifetimes. For many rare diseases, little is known."
The NIH is also working closely with the Center for Orphan Disease Research and Therapy at Penn, which was launched with an anonymous $10 million gift in 2011. The center is creating partnerships with academic medical centers around the country, as well as with pharmaceutical and biotech companies.
Such collaboration may lead to treatment breakthroughs, as big pharma is increasingly interested in niche markets. Some advances may result from identifying drugs developed for other purposes that work on the same biological mechanisms. "Pharmaceutical companies have perfectly safe drugs that have been pulled from the market," says the Perelman School of Medicine's Glenn Gaulton. "Perhaps the drugs weren't financially viable, but our goal is to provide researchers access to those drugs and to the data."