Gaucher disease is a rare, inherited disorder that causes fatty substances to build up in the spleen, liver, and other organs.

Finding a doctor to diagnose Gaucher disease can sometimes be a frustrating experience for patients. They typically go from one specialist to another and get sicker and sicker as the doctors scratch their heads.

At Yale Medicine, we have experts ready to help, and patients come to us from around the country for our expertise in Gaucher disease. It is the most common lyosomal storage disease, a family of inherited metabolic disorders that originate in the lysosomes, or parts of the cell that help with digestion.

“We have an internationally recognized program and a national referral base with incredible models of precision medicine and innovative therapies,” says Yale Medicine’s Pramod K. Mistry, MD, PhD, director of Lyosomal Disease & Inherited Metabolic Liver Disease Program. “People come to us because they have very complicated aspects that no one else can figure out.”

Gaucher disease is a rare, inherited disorder where fatty cells build up in areas including the liver, spleen, and bone tissue and marrow. The organs enlarge—sometimes as much as 50 times its normal size for the spleen—and bones are affected, which increases the risk of fracture and severe bone pain (called a “bone crisis”) that requires joint replacement. The disease is caused by the body not having enough of an important enzyme (glucocerebrosidase), which breaks down a fatty chemical (glucocerebroside).

Gaucher disease is divided into three main categories:

• Type 1 is the most common form of the disorder in Western countries, constituting approximately 95 percent of patients.
• Type 2 is rare and is associated with severe neurological abnormalities and is usually fatal within the first two years of onset.
• Type 3 is rare in the United States and Europe, but it is the most common form of the disease around the world. It has the same symptoms as type 1, plus some neurological damage.

Worldwide, Gaucher disease affects 1 in 40,000 people, but its frequency is as high as 1 in 450 people among Jews of Ashkenazi (Eastern European) descent. Although it is present at birth, symptoms can appear at any age.

Research shows that patients with Gaucher disease type 1 may be at increased risk of developing other conditions, usually after age 50. These include:

• Parkinson disease
• Some cancer types, including multiple myeloma (a blood cancer) and liver cancer

To have Gaucher disease, you must have two mutations of a gene called GBA: one from your mother and one from your father. But you can be a carrier and have just one mutation related to the disorder and not have Gaucher disease.

If both parents are carriers, each pregnancy has a 1 in 4 chance that the baby will have the disease. Today, prenatal testing can be done early in the pregnancy, which people with a family history of the disease may want to consider.

Symptoms of Gaucher disease type 1 can differ vastly and can range from severe to none at all. Some signs include:

• Swollen belly (from spleen and liver enlargement)
• Bone pain and easily fractured bones
• Anemia (low red blood cell counts) and fatigue
• Bleeding (frequent nosebleeds, gum bleeding) and bruising problems (caused by decrease in blood platelets)

Because the signs and symptoms of Gaucher disease—including bone pain and anemia—can resemble many other diseases and conditions, it can often go diagnosed for many years. Here are some diagnostics that may be used:

• Physical exam: Your doctor can press on your abdomen to check the size of your spleen and liver.
• Lab tests: Blood tests can check for levels of the enzyme linked to Gaucher.
• Imaging tests: Dual energy X-ray absorptiometry (DXA) uses low-level X-rays to measure bone density. Magnetic resonance imaging (MRI) can show if the spleen or liver is enlarged and if bone marrow has been affected. We also do echocardiograms and EKGs to see if the lungs or heart are involved.
• Genetic tests: These can reveal whether you have the disease.

At Yale Medicine, we conduct all of our initial diagnostic and evaluation tests in our medical offices during a single visit.

Type 1 Gaucher disease, as well as the non-neurological symptoms of type 3, are treatable. Available therapies include:

• Enzyme replacement therapy (ERT): This balances the low levels of glucocerebrosidase, which is the underlying cause of Gaucher disease. Patients receive intravenous infusions of the enzyme every two weeks.
• Substrate reduction therapy (SRT): This is an oral medication that decreases the rate of formation of glucocerebroside in the body so that excess buildup is reduced.

At Yale Medicine, our multidisciplinary team of experts treat all three types of Gaucher disease. We offer the most up-to-date patient care and research.

Yale researchers have been at the forefront of research efforts worldwide. In 2010, Dr. Mistry was the lead author on a study that unraveled some of the biological actions that can trigger the disease, thereby leading the way toward potentially more effective and less expensive treatments.

Yale is also at the forefront of innovative therapies for Gaucher disease. Dr. Mistry led an international study of oral SRT that was published in the Journal of the American Medical Association in 2015 and had since been approved by the FDA.

Yale’s research efforts not only enhance treatment of patients with rare diseases, but they lead to improved understanding of common diseases such as myeloma and Parkinson’s and potential new treatment approaches for them.

“We have patients from as far as Texas and California. We are very active in patient support and building a network,” Dr. Mistry says, adding that helping patients who maybe went years with mysterious symptoms no one could pinpoint is rewarding. “Every time I meet one of these families and see how much suffering they have been through, it moves me.”