When Doctors Encounter Diseases without Names

The complicated meaty machine that is the human body can break down in a remarkable variety of ways. The 9th edition of the International Classification of Diseases (ICD-9) includes more than 16,000 afflictions – everything from the bite of a venomous tropical millipede to injury by falling spacecraft debris.

With all of these dangers, it is truly a wonder that any of us can get out of bed in the morning. And yet any doctor who cares for patients knows that there are many other diseases that ICD-9 has never heard of – medical terra incognita, disorders that have yet to be defined or clearly described.

My colleagues and I are regularly asked to consult on patients with peculiar problems that don’t fit textbook depictions of any known disease, or where there is confusion because several similar diagnoses would fit equally well. Some of these patients have unusual manifestations of well-known medical conditions, but others may suffer from entirely new entities.

Lynne is one such patient with a murky malady. She’s a globetrotting academic whose frequent-flyer-mile accumulation rate dropped after she was diagnosed with an unusual form of anemia called sideroblastic anemia, which she could either have been born with or could have acquired.

Existing tests could not distinguish between these possibilities, and without knowing where the disease originated, no one could tell Lynne what to expect or predict how her condition might evolve.

When I first saw Lynne in Dana-Farber’s Center for Hematologic Oncology, she allowed me to save some extra cells from her blood and bone marrow for future research.

A few months later, at an international symposium in Scotland in May 2011, I heard a European scientist talk about a novel mutation in a gene called SF3B1 that she’d just found in blood cells from people with a form of myelodysplastic syndrome (MDS) that resembled Lynne’s condition.

When I got back to Boston, I called my friend Dr. Rafael Bejar, an extraordinarily talented scientist currently working in the laboratory of Dr. Ben Ebert at Brigham and Women’s Hospital. Raf had met Lynne and knew all the details of her problem. Raf said he could examine DNA from Lynne’s stored cells and look for this new mutation.

Raf found that Lynne’s blood cells have the most common (K700E) mutation in SF3B1, clearly identifying her condition as an unusual type of MDS called refractory anemia with ring sideroblasts. The rest of her cells have normal SF3B1, which meant she wasn’t born with this, and couldn’t have passed it on to her children. Some early reports suggest that this mutation confers a good prognosis.

Lynne was pleased to learn about the molecular clarification of her diagnosis, which we were able to tell her about months before the first papers on these mutations appeared in print in the journals Nature and The New England Journal of Medicine. It will likely be some time before any for-profit clinical lab offers testing for mutations in this gene.

Now we have assembled a collection of cells from other patients with unusual forms of anemia who don’t have SF3B1 or any other known mutation. In collaboration with Dr. Mark Fleming at Boston Children’s Hospital and several other researchers, we’re on the verge of defining several brand-new maladies at the molecular level.

I’ve worked previously at clinical institutions where parking was easier and my daily commute was less painful than it is now. Those hospitals were fantastic places in many respects. But the ability to collaborate with scientists just across the street who are of the caliber of Raf, Ben, and Mark – people who are both brilliant, and enthusiastic about studying patients with the same conditions that I want to understand better – was more limited there.

This is something unique about Dana-Farber: Patients and their doctors have access to a vibrant cohort of scientific collaborators who are second to none in the world, who are making discoveries in real time, and can bring a ray of light where there is darkness.

David P. Steensma, MD, FACP, is a physician in Dana-Farber’s Hematologic Oncology Treatment Center.