By official definition, a rare disease is a condition that afflicts less than 200,000 people in the United States, or roughly the combined populations of El Cajon and Vista.
Scientists have documented more than 10,000 rare diseases, with unfamiliar names ranging from abetalipoproteinemia to Zollinger-Ellison syndrome. Some diseases for fewer than a dozen known cases worldwide.
But taken altogether, rare diseases affect about 30 million people in the United States alone — or about one in 10. That’s approaching the ubiquity of diabetes, which affects more than 38 million Americans, diagnosed and undiagnosed. Total rare-disease numbers worldwide are estimated to be 300 million to 400 million.
Rarity is a curse. The most difficult aspect of being stricken by a rare disease may be the difficulty in getting a correct diagnosis. Few frontline physicians have a working knowledge of every rare disease, or even some of them. Having never treated most, if any, rare diseases in practice, they likely do not recognize tell-tale symptoms or know what specific actions to take.
As a result, patients with rare diseases are frequently misdiagnosed or undiagnosed. On average, they wait nine years to finally receive an accurate diagnosis. That figure hasn’t changed in 45 years.
Half of all rare-disease cases involve children, of whom one-third will die before they are 5 years old — before doctors even figure out what killed them.
But a correct diagnosis may offer little solace. There are no approved therapies for 95 percent of rare diseases, few tested tools in the armamentarium, no go-to remedies. Most options are off-label, experimental or “Let’s try this.” If you have a rare disease, you likely will have it, probably unabated, for the rest of your abbreviated life.
That’s a harsh reality, but it is leavened by hope. Patients and their caregivers live on hope, which is fueled by this fact: Roughly 80 percent of rare diseases have a genetic basis, and advances in genomic sequencing technologies and molecular gene therapies are improving diagnostic tools.
Progress in developing treatments is more challenging. Traditional clinical trials, which typically require hundreds or thousands of participants, are problematic. The U.S. Food and Drug istration has recognized that novel approaches are needed, such as modified or adaptive trials and the use of innovative gene and cell therapies. That’s good news.
But health inequities are more pronounced. Lack of access to the latest and best tools, such as newborn screenings and genetic testing, helps ensure poorer outcomes for some patients with rare diseases.
Since 2008, Rare Disease Day has been held around the world on the last day of February. This year — a leap year — it will be Thursday, Feb. 29, the rarest of calendar dates. It is a day to take note of rare-disease patients and their caregivers and maybe take action.
On March 1-3, Sanford Burnham Prebys will host its annual scientific and family symposium on congenital disorders of glycosylation or CDG, an umbrella term that covers more than 190 rare (fewer than 2,000 children worldwide) genetic diseases involving a complex chemical process called glycosylation. When this metabolic process, which involves attaching essential sugar molecules to proteins, doesn’t work correctly, numerous, often severe, consequences in infancy and childhood occur, from poor growth and developmental delays to stroke-like episodes and heart problems.
Life expectancy for someone with congenital disorders of glycosylation ranges widely. In one published survey of one form of CDG, the age of death ranged from 15 days to 48 years, with a median age of 2 years. In another, the mortality rate was 20 percent in the first four years of life.
Hudson Freeze, director of the Sanford Children’s Health Research Center at Sanford Burnham Prebys, has been working on congenital disorders of glycosylation for more than a quarter-century. The institute is an international hub for CDG research.
But too much of current rare-disease research remains siloed and organized around single disorders, which hinders everything from sharing data and ideas to conducting effective clinical trials.
Every day should be a rare-disease day, bringing together clinicians, scientists, technicians, funders, educators, families and others to broadly and directly remedy diseases that numerically affect very few.
We owe it to every rare-disease patient who cannot afford to be patient.
Dr. David Brenner is a physician-scientist and president and chief executive of the La Jolla-based Sanford Burnham Prebys medical research institute. He lives in La Jolla. ◆
