Gaucher Disease: Yale Offers New Insights, Treatment, and Hope

Nathaniel Kleytman was 5 years old when his bones began to mysteriously fracture for no apparent reason. For years, he limped about in pain, while doctors tried in vain to figure out what was going on. They tested him for dozens of diseases, including rheumatoid arthritis, leukemia, and other types of cancer. The tests all came back negative.

Meanwhile, the debilitating problems continued. At one point, Kleytman was bedridden for 10 months, forced to wear a brace for 18 to 20 hours per day. His orthopaedic surgeon told him, “Nate, you are an enigma.” That, Kleytman says, is the “last person you want to hear that from.”

Finally, at age 14, Kleytman was diagnosed with Gaucher disease, a rare genetic condition that causes an enzyme deficiency in the lysosomes of cells. Because of the deficiency, lipids (a type of fatty substance) accumulate in organs throughout the body, causing a wide array of symptoms. Many Gaucher patients have enlarged livers or spleens, for example, or for others, like Kleytman, lipids build up in the bone marrow, which leads to pain and fractures.

Unfortunately, Kleytman’s saga of searching for answers is “not the exception; it is the rule,” says Pramod Mistry, MD, director of the Yale Gaucher Center for Lysosomal Diseases. “Families who are affected by rare diseases really don’t have an expert doctor to go to or have continuity of care.”

At Yale, Dr. Mistry and colleagues are at the forefront of discovering the biological mechanisms behind Gaucher and other lysosomal diseases—and discovering new treatments. One treatment, which Yale took the lead role in developing, is a drug called a substrate inhibitor—an oral medication that helps decrease the buildup of a certain enzyme.

Remarkably, the use of substrate inhibitors has led to some promising findings regarding multiple myeloma, which Gaucher patients often develop. “Here is a rare disease that is illuminating a common disease. And I can tell you the same story with Parkinson disease,” Dr. Mistry says.

Gaucher patients have a twentyfold risk of developing Parkinson’s disease; Yale researchers are exploring the Gaucher gene that is linked to the neurodegenerative disorder.

While Dr. Mistry and his colleagues continue to make important discoveries about both rare and common diseases, they don’t lose sight of patients like Kleytman, who is now a Yale School of Medicine student studying Gaucher disease.

At Yale, patient care and research are so closely connected that scientific findings are integrated into clinical care. “The patient should be the center of everything you do. You can't compartmentalize being a clinician and being a researcher,” says Tamar Taddei, MD, director of the Regional Liver Cancer Program. “If you capture all of the information that your patients give you, you can uncover groundbreaking questions that can change their lives.”

And no patient, Dr. Mistry says, should ever be an enigma. “We should be able to get to the root cause of their ill health and fix it,” he says.

In this video, Dr. Mistry and fellow researchers and clinicians talk more about their effort to care for Gaucher patients and others with rare diseases.