Monoclonal gammopathy of undetermined significance (MGUS) is a condition in which an abnormal protein (monoclonal protein, or M protein) is in the blood. M protein is produced by plasma cells, a type of white blood cell. Monoclonal gammopathy of undetermined significance usually causes no problems. Sometimes, monoclonal gammopathy of undetermined significance is either associated with another disease or can progress over years to other disorders, including some forms of blood cancer.

If you have monoclonal gammopathy of undetermined significance, you'll usually have periodic checkups to monitor your level of M protein. If there's no increase, monoclonal gammopathy doesn't require treatment.

With close monitoring, if monoclonal gammopathy of undetermined significance does progress, you'll get earlier treatment.

Monoclonal gammopathy of undetermined significance rarely causes signs or symptoms. The condition is usually detected by chance when you have a routine blood test for another problem. However, some people may experience nerve problems, such as numbness or tingling, associated with the abnormal protein.

Monoclonal gammopathy of undetermined significance occurs when plasma cells in your bone marrow produce an abnormal protein called monoclonal protein (M protein). Plasma cells are a type of white blood cell. They are found in your bone marrow. Plasma cells produce some of the antibodies that help your body fight infection.

In the majority of people with monoclonal gammopathy of undetermined significance, the protein isn't harmful. But when too much M protein accumulates, it crowds out healthy cells in your bone marrow and can damage other tissues in your body.

Genetic changes appear to play a role in monoclonal gammopathy of undetermined significance, as do environmental triggers.

Factors that increase your risk of monoclonal gammopathy of undetermined significance include:

  • Your age. The risk of monoclonal gammopathy of undetermined significance increases as you get older. The highest incidence is among adults age 85 and older.
  • Your race. Blacks are more likely to experience this condition than are whites.
  • Your sex. Monoclonal gammopathy of undetermined significance is more common in men than it is in women.
  • A family history. If other people in your family have monoclonal gammopathy of undetermined significance, your risk of developing the disorder may be higher.

Some people with monoclonal gammopathy of undetermined significance develop a more serious condition, such as multiple myeloma or other cancers or blood disorders.

Doctors can't definitively predict who will go on to develop a more serious condition, but they can determine who has the greatest risk. Your doctor takes into account several factors when determining your risk, including:

  • The amount of M protein in your blood
  • The type of M protein
  • The amount of another small protein (free light chain) in your blood

Your risk of developing a more serious condition increases the longer you've had monoclonal gammopathy of undetermined significance. Also, the more risk factors you have, the higher your risk of developing a more serious condition.

Other complications associated with monoclonal gammopathy of undetermined significance include fractures and blood clots.

Most often, monoclonal gammopathy is detected and monitored with blood tests. These tests require no preparation on your part. If you're found to have monoclonal gammopathy of undetermined significance, you may be referred to a doctor who specializes in blood disorders (hematologist).

It's a good idea to arrive well prepared for your appointment. Here's some information to help you get ready, and what you might expect from your doctor.

What you can do

  • Write down any symptoms you're experiencing, including any that may seem unrelated to the reason for which you scheduled the appointment.
  • Write down key personal information, including any major stresses or recent life changes.
  • Make a list of all medications, vitamins or supplements that you're taking. Or bring the original bottles your medications came in with you.
  • Ask a family member or friend to come with you. Sometimes it can be difficult to remember all of the information provided to you during an appointment. Someone who accompanies you may remember something that you missed or forgot.
  • Write down questions to ask your doctor.

Your time with your doctor is limited, so preparing a list of questions can help you make the most of your time together. List your questions from most important to least important in case time runs out. For monoclonal gammopathy of undetermined significance, some basic questions include:

  • What kinds of tests do I need? Do these tests require any special preparation?
  • How frequently do I need to be tested?
  • Can I have a copy of my blood test results?
  • Is this condition temporary or long lasting?
  • What treatments are available?
  • I have other health conditions. How can I best manage these conditions together?
  • Are there any lifestyle changes I can make, such as changing my diet, that might help?
  • How frequently do I need to schedule follow-up visits?
  • Are there any brochures or other printed material that I can take with me? What websites do you recommend?

In addition to the questions that you've prepared to ask your doctor, don't hesitate to ask additional questions during your appointment.

What to expect from your doctor

Your doctor is likely to ask you a number of questions. Being ready to answer them may reserve time to go over points you want to spend more time on. Your doctor may ask:

  • Are you experiencing any symptoms?
  • Do you have a family history of monoclonal gammopathy of undetermined significance?
  • Have you ever had cancer?
  • Do you have any numbness or tingling in your hands and feet?
  • Have you ever had a blood clot?
  • Have you ever experienced a broken bone?
  • Do you have osteoporosis?

Monoclonal gammopathy of undetermined significance is usually detected during a blood test for another condition or other symptom, such as a nerve condition called peripheral neuropathy or an unexplained rash. The test, called serum protein electrophoresis (SPE), separates your blood proteins into five parts and can show any abnormal proteins as well as unusual amounts of normal proteins. Another test, the free light chain assay, is often done at the same time as the SPE, and it looks at the smaller parts of the M protein.

If your doctor detects monoclonal gammopathy, further testing may be ordered to determine what M protein your body is making and how much is being made. Your doctor also works to rule out other causes of elevated protein levels. Tests may include:

  • Blood tests. Tests to count the blood cells in your blood (complete blood count), to look for decline in kidney function (serum creatinine test) and to determine the amount of calcium in your blood (serum calcium test) can help rule out other types of monoclonal gammopathy, such as multiple myeloma.
  • Urine tests. Urine tests may be performed to determine if the abnormal protein is being released in the urine or to diagnose any kidney damage as a result of the protein. You'll likely need to collect your urine for 24 hours for this test.
  • X-rays. X-rays help your doctor look for bone abnormalities that may indicate another type of plasma cell disorder.
  • Bone marrow test. During a bone marrow test, your doctor uses a hollow needle to remove a portion of your bone marrow from the back of one of your hipbones. The bone marrow is then analyzed to determine what percentage of plasma cells it contains. This test is generally only done when doctors suspect that someone is at risk of developing a more serious disease, or in people with unexplained anemia, kidney failure, bone lesions or high calcium levels.

Monoclonal gammopathy of undetermined significance doesn't require treatment, but your doctor is likely to recommend periodic checkups to monitor your health.

A checkup six months after diagnosis may be appropriate for most people. If you have a high risk of developing a more serious condition, your doctor may recommend more frequent checkups so that if a disease such as multiple myeloma develops, it can be treated as early as possible. Ask your doctor how often you need to be seen.

A risk-assessment model can predict the risk of progression to multiple myeloma. This model uses the size and type of the abnormal protein and a special blood test called the serum free light chain assay.

If you have monoclonal gammopathy of undetermined significance and bone loss, your doctor may recommend treatment with medications called bisphosphonates that help increase your bone density. Examples of bisphosphonates include alendronate (Binosto, Fosamax), risedronate (Actonel, Atelvia), ibandronate (Boniva) and zoledronic acid (Reclast, Zometa).

Although you can't control whether monoclonal gammopathy of undetermined significance will lead to something more serious, you can control many aspects of your health. The following suggestions may help:

  • Learn what you can about monoclonal gammopathy of undetermined significance. Write down questions that come up and ask your doctor about them during your next appointment. Ask your health care team about resources for more information. The better you understand what's going on in your body, the more you may be able to take an active role in your health care.
  • Control what you can about your health. Living a healthy lifestyle may not reduce your risk of complications in the future, but it can make you feel better and reduce your risk of other diseases and conditions. Eat a variety of fruits and vegetables. Get regular exercise. Get enough sleep so that you wake feeling rested. Reduce the amount of stress in your life.
  • Stick to your checkup schedule. Follow your checkup schedule and get the tests to monitor for more-serious diseases. Though you might be nervous about receiving your test results, diagnosing a serious condition, such as cancer, in the early stages may improve your chance for a cure.

Right now, the cause of monoclonal gammopathy of undetermined significance is unknown, so there is no way to prevent monoclonal gammopathy of undetermined significance and no way to stop it from progressing to a more serious condition.

  • Experience. Mayo Clinic hematologists diagnose and care for hundreds of patients with monoclonal gammopathy of undetermined significance (MGUS) each year. Experienced pathologists are skilled in the testing and identification of the M protein and determining its potential risk of progression to cancer.
  • Research Advances. Numerous Mayo Clinic researchers are studying MGUS to better understand it and to improve treatment options. Mayo Clinic researchers developed a risk-assessment model that can predict risk of progression of monoclonal gammopathy of undetermined significance to multiple myeloma.
  • Coordinated care. A specialist in blood diseases (hematologist) will oversee your care and bring in other specialists as needed, including neurologists if nerve damage is suspected, nephrologists to prevent kidney failure and dermatologists if skin lesions occur. Access to specialists, testing and treatment is available in one convenient location and can be accomplished in a few days.

At Mayo Clinic, we assemble a team of specialists who take the time to listen and thoroughly understand your health issues and concerns. We tailor the care you receive to your personal health care needs. You can trust our specialists to collaborate and offer you the best possible outcomes, safety and service.

Mayo Clinic is a not-for-profit medical institution that reinvests all earnings into improving medical practice, research and education. We're constantly involved in innovation and medical research, finding solutions to improve your care and quality of life. Your doctor or someone on your medical team is likely involved in research related to your condition.

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Researchers at Mayo Clinic coined the term "monoclonal gammopathy of undetermined significance" (MGUS) when they originally identified this condition. Mayo Clinic researchers are studying MGUS to better understand it and to improve treatment options.

Mayo Clinic researchers are actively studying the epidemiology of monoclonal gammopathy of undetermined significance. That means they're looking at how many people have the condition, and what the risk factors are for developing monoclonal gammopathy of undetermined significance. They're also studying how risk factors for the disease may influence its treatment.

A risk-assessment model has been developed by Mayo Clinic researchers. It can predict risk of progression of MGUS to multiple myeloma. Mayo Clinic is also studying ways of preventing progression of monoclonal gammopathy of undetermined significance to myeloma.

Doctors and scientists in the Hematology Program of the Mayo Clinic Cancer Center are working on improving the diagnosis and treatment of myeloma and other blood disorders. Learn about research in the Mayo Clinic Hematologic Malignancies Program.

Laboratory scientists at Mayo Clinic continue to study the roles that genetic factors, growth factors for cells (cytokines) and new blood vessel formation (angiogenesis) play in the initiation and progression of monoclonal gammopathy of undetermined significance.

Publications

See a list of publications by Mayo Clinic doctors on monoclonal gammopathy of undetermined significance on PubMed, a service of the National Library of Medicine.

May 17, 2013