Gaucher disease is a rare genetic disorder that affects up to 1 in 100,000 infants born in the United States. For those with Ashkenazi Jewish heritage —Jews whose ancestors are from Eastern Europe — the incidence of Gaucher disease is about 1 in 450 births, but as many as 1 in 10 Ashkenazi Jews may carry the genetic mutation responsible for the condition.
Four states – Illinois, Missouri, New Jersey and Tennessee – require newborn testing for Gaucher disease. Early identification through newborn or later genetic screening are important because the disease is progressive and, without proper treatment, can cause irreversible damage to organs and bones.
“It used to be, ‘Oh, this is a childhood pediatric disease.’ But we are seeing it in our care center,” says Marlon Kleinman, M.D., a hematologic oncologist at City of Hope® Cancer Care North Shore in Morton’s Grove, an area of Illinois with a high population of Ashkenazi Jews. “One of the reasons we are interested in Gaucher disease as hematology oncology doctors is that research has shown it can increase the risk in the adult for blood cancers.”
In this article, we’ll explore:
- What is Gaucher disease?
- What causes Gaucher disease?
- Gaucher disease and cancer risk
- Treating Gaucher disease
- Managing Gaucher Disease at City of Hope
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What Is Gaucher Disease?
Gaucher disease, named for French physician Philippe Charles Ernest Gaucher, who first identified the condition in 1882, is a metabolic disorder in which cells do not produce an important enzyme that helps clean out or recycle a fatty substance found in cells called glucocerebroside.
“This enzyme — glucocerebrosidase — is missing in patients with Gaucher disease, which causes a buildup of the chemical glucocerebroside and other fatty-like chemicals.
“It’s sort of like half-baked brownies, if you will,” explains Dr. Kleinman. “So, there are these incomplete, fatty and sugary like chemicals that normally would become some important functional or structural parts of that cell that never get to exist and everything builds up.”
Over time, the accumulation of these substances can lead to cellular and tissue damage particularly in the liver and spleen and in bone marrow. A rarer type of Gaucher disease may also have an impact on the nervous system and affect the brain.
Patients with the most common type of Gaucher disease — Type I — may have symptoms including an enlarged spleen, liver or both, a condition called hepatosplenomegaly. They may bruise easily due to thrombocytopenia, or low blood platelet count. They may also feel tired and fatigued due to anemia and may experience chronic bone pain.
Less common types II and III Gaucher disease usually affect infants and, in addition to symptoms like an enlarged spleen and liver, patients may have bone deformities, liver malfunction and neurologic symptoms. Life expectancy is short with type II Gaucher disease.
“The one that affects the Ashkenazi community the most is type I,” says Dr. Kleinman, adding that each case is unique, and symptoms and severity can vary widely.
What Causes Gaucher Disease?
Gaucher disease is what’s called an autosomal recessive disorder, which means to actually have the disease, a person must inherit a mutated GBA gene from each parent to make a pair of abnormal GBA genes.
If only one of the pair of a person’s GBA genes is mutated, the person is considered a carrier but will not have the condition or any symptoms. If both parents are carriers of the mutated gene, there is a one in four likelihood that their child would have Gaucher disease. This diagram from the National Gaucher Foundation explains the various genetic combinations and likelihood of inheriting Gaucher disease.
While anyone can inherit Gaucher disease, it is the most prevalent inherited genetic disease for Ashkenazi Jews, according to the National Gaucher Foundation, with an estimated 1 in 10 Ashkenazi Jews being possible carriers.
In states that do not have routine infant screenings for Gaucher disease, those of Ashkenazi descent may want to consider genetic screening and counseling to determine if they are a carrier.
Gaucher Disease and Cancer Risk
Dr. Kleinman describes an unusual case he saw in his clinic that underlined for him the link between Gaucher disease and certain types of cancer.
A woman presented with an enormous spleen and low blood counts. As Dr. Kleinman worked to find a diagnosis, he learned that the woman’s grandson had Gaucher disease.
“Being a very smart woman, she dug deeper through research and she was convinced that she had active Gaucher disease,” Dr. Kleinman says. She got genetic testing and discovered that indeed she had type 1 Gaucher disease herself.
“So, this is like reverse family counseling,” he says. “Here one of her grandchildren was initially recognized as a Gaucher patient.”
After performing other diagnostic tests, Dr. Kleinman made the definitive diagnosis that the patient had myelofibrosis, a type of chronic leukemia.
“What we're learning about Gaucher is it increases the risk in the adult for blood cancers and myelofibrosis is one of them,” Dr. Kleinman says. “It's not the most common. Most commonly we see multiple myeloma — there’s a high incidence of multiple myeloma in Gaucher survivors. But everything is fair game — including myeloma, lymphoma, leukemia.”
In addition to blood cancers like those described by Dr. Kleinman, researchers have found a link between Gaucher disease and increased incidence of liver cancer as well as to Parkinson’s disease and osteoporosis.
Most people with Gaucher disease will not develop cancer, Parkinson’s disease or osteoporosis, but the risk is slightly elevated when compared to the general population.
Luckily, treatments for Gaucher disease may lower the risk of developing any associated conditions.
Treating Gaucher Disease
Treating Gaucher disease may reduce symptoms and help prevent any permanent damage to organs.
Currently, doctors employ two basic strategies, according to Dr. Kleinman:
- Enzyme replacement therapy (ERT)
- Substrate reduction therapy (SRT)
ERT is just what it sounds like — drugs that replace the crucial missing glucocerebrosidase enzyme. The U.S. Food and Drug Administration (FDA) has approved three ERT drugs that are given intravenously.
“They’ve been through various clinical trials and been shown to be very effective,” Dr. Kleinman says. “When they’re started earlier in life, a lot of the complications seem to be reduced.”
SRT uses a different approach by reducing the amount of the fatty substance or glucocerebroside the missing enzyme would need to break down. Two orally administered drugs are available to be used in SRT.
“So, that’s what treats the disease, but the cancers that may result from it, that would be a completely different type of treatment depending on what that cancer is,” Dr. Kleinman clarifies.
Managing Gaucher Disease at City of Hope
Researchers at City of Hope in Duarte, California were among the pioneers in developing ERT for Gaucher disease in the 1970s.
Today, at City of Hope Morton Grove and throughout the City of Hope national network of hospitals and care centers, clinicians are helping patients with active Gaucher disease manage the condition and screen regularly for any signs of cancer.
Those whose ancestry may make them at higher risk of Gaucher disease may consider genetic screening and counseling, which is available at City of Hope, where clinicians are finely attuned to the research linking Gaucher disease to elevated risk of cancer and other conditions.
If you or a loved one has been diagnosed with cancer and are looking for a second opinion, call us 24/7 at 877-524-4673.