Rare Insight

In October, Suffolk University Biochemistry Chair and Professor Melanie Berkmen received a plea from the parent of a child with a rare and incurable disease called fumarase deficiency.  

Would Berkmen and her students be willing to study the child’s genetic mutations? And in learning about this patient, could they produce data that might someday help others? 

For Berkmen, the answer was an easy “yes.”  

In 2013, she’d been the one searching for answers after she lost her beloved 14-year-old niece, Lara, to leukemia. To honor Lara’s memory, Berkmen vowed to use her skills to contribute to research that would help other children. She realized that while she might not be able to tackle cancer in her small lab, she could devote her efforts to a little-studied rare disease with effects that can be just as devastating.  

Fumarase is a metabolic protein that’s responsible for converting food into energy. It’s also what’s known as a tumor suppressor protein, says Berkmen, “which means that if you get mutations in it, it increases your chances of developing cancer or a tumor.” Babies born with fumarase deficiency can experience failure to thrive, developmental delays, seizures, and a host of serious neurological impacts. The condition is often fatal in childhood. It’s also extremely rare, with physicians reporting approximately 100 cases worldwide, and at present has no known cure. 

For an uncommon disease like fumarase deficiency, giving researchers additional data on even a single new patient’s mutation might provide clues to potential treatments. That’s where Berkmen and her students come in.  

For nearly a decade, they have been studying clinically relevant mutations in the fumarase protein. They purify and characterize the fumarase variants, which can shed light on the biochemical underpinnings of the disease. What began as a short unit in her Advanced Biochemistry Research Lab class has grown into a semester-long project every spring.  

Initially, they used case files that had been published in scientific literature, studying the biochemical effects of particular patients’ mutations. Then one day Berkmen got an unexpected call. A former student, Olivia Grocott, BS ’15, who’d worked on the research project in her lab class at Suffolk was now working with a fumarase deficiency patient at Massachusetts General Hospital.  

“I got to meet the patient and her amazing mother, and I spoke with her care team,” says Berkmen. Then she and her students collaborated with Grocott on a paper analyzing the patient’s disease. “Olivia wrote the portion about the symptoms and the diagnosis, and then my research students and I did the biochemical analysis.”  

This semester, working with protected patient information required Berkmen and her students to comply with patient confidentiality requirements in a process approved by Suffolk’s Institutional Review Board. Jennifer Pham, an honors biochemistry student working with Berkmen who will graduate in May, says learning to properly handle patient data is critical for students like her who hope to enter the highly regulated and deeply rewarding world of biomedical research. It’s also taught her firsthand why it’s important to study rare diseases. 

“Rare conditions can significantly impact not only the lives of patients, but also their families and communities,” says Pham. “As we build our own knowledge about fumarase deficiency, we also get to make a contribution to the scientific community by expanding what little is already known.” 

According to the National Institutes of Health, more than 10,000 rare diseases—each affecting relatively few people—collectively account for millions of American patients. Yet most research efforts (and dollars) focus primarily on common conditions like diabetes, cancer, or obesity, says Berkmen. 

The team has published two papers analyzing four different mutations, adding substantively to the scant scientific data on the disease. Now that Berkmen is becoming recognized as an expert in this work, families are starting to call.  

“We cannot treat or cure their child, but we can help them understand this disease better,” explains Berkmen. Perhaps the most important result of Berkmen’s research will be how it inspires a new crop of biochemists to pay attention to rare diseases.  

“Many of my students want to go to medical school, so working on something medically relevant is exciting,” says Berkmen.    

“I think my major contribution is training the next generation of scientists who now have an interest in rare diseases and have the biochemical toolkit and skills to someday help find cures.”