Monoclonal gammopathy of undetermined significance (MGUS) is a condition in which an abnormal protein — known as monoclonal protein or M protein — is in your blood. The protein is produced in a type of white blood cell (plasma cells) in your bone marrow.

MGUS usually causes no problems. But sometimes it can progress over years to other disorders, including some forms of blood cancer.

It's important to have regular checkups to closely monitor monoclonal gammopathy so that if it does progress, you get earlier treatment. If there's no disease progression, MGUS doesn't require treatment.

People with monoclonal gammopathy generally don't experience signs or symptoms. Some people may experience a rash or nerve problems, such as numbness or tingling. MGUS is usually detected by chance when you have a blood test for another condition.

MGUS occurs when abnormal plasma cells produce M protein. The protein isn't harmful for most people. But if too much M protein accumulates, it crowds out healthy cells in your bone marrow and can damage other tissues in your body.

The precise cause of accumulating M protein isn't known. Genetic changes and environmental triggers appear to play a role.

Factors that increase your risk of developing MGUS include:

  • Age. The average age at diagnosis is 70 years.
  • Race. Africans and African-Americans are more likely to experience MGUS than are white people. The incidence in other races isn't clear.
  • Sex. MGUS is more common in men.
  • Family history. You may have a higher risk of MGUS if other people in your family have the condition.

Each year about 1 percent of people with MGUS go on to develop a more-serious disorder. The conditions that can develop depend on the type of MGUS you have:

  • Non-IgM MGUS (IgG, IgA or IgD MGUS). This is the most common type of MGUS and has the potential to progress to multiple myeloma. Less frequently, people with Non-IgM MGUS can progress to other disorders, such as immunoglobulin light chain (AL) amyloidosis or light chain deposition disease.
  • IgM MGUS. About 15 percent of people diagnosed with MGUS have IgM MGUS. It can progress to a certain rare cancer (Waldenstrom macroglobulinemia) and, less often, to lymphoma, AL amyloidosis or multiple myeloma.
  • Light chain MGUS (LC-MGUS). This newly classified type of MGUS can progress to a condition in which a certain type of M protein is in your urine (Bence Jones proteinuria) and to light chain multiple myeloma, AL amyloidosis or light chain deposition disease.

To determine your risk of progression, your doctor will consider:

  • The size and type of M proteins in your blood.
  • The amount of another small protein (free light chain) in your blood.
  • Your age at diagnosis. Your risk of developing a more serious condition increases the longer you've had MGUS.

Other complications associated with MGUS include bone fractures, blood clots and kidney problems.

MGUS is usually detected during blood tests for another condition, such as a certain nerve disorder (peripheral neuropathy). The blood tests can show abnormal proteins as well as unusual amounts of normal proteins.

If your doctor detects monoclonal gammopathy, further testing may be recommended to determine which M protein your body is making and how much is being made.

To rule out other causes of elevated protein levels, your doctor might recommend:

  • Additional blood tests. Tests to count the blood cells in your blood (complete blood count), to look for a decline in kidney function (serum creatinine test) and to determine the amount of calcium in your blood (serum calcium test) can help rule out conditions such as multiple myeloma.
  • Urine tests. These tests can determine if abnormal protein is being released into your urine, and assess any resulting kidney damage. You'll likely need to collect your urine for 24 hours.
  • Imaging tests. If you are experiencing bone pain, your doctor might recommend an MRI or CT-positron emission tomography (PET) scan. The images can help your doctor find bone abnormalities related to MGUS.
  • Bone marrow test. A hollow needle removes a portion of your bone marrow from the back of one of your hipbones. The bone marrow is analyzed to determine its percentage of plasma cells. Bone marrow testing is generally done only when you're at risk of developing a more serious disease or if you have unexplained anemia, kidney failure, bone lesions or high calcium levels.

MGUS doesn't require treatment. But your doctor is likely to recommend periodic checkups to monitor your health, probably starting six months after your diagnosis.

Watchful waiting

If you are at high risk of developing a more-serious condition, your doctor may recommend more frequent checkups so that any progression can be diagnosed and treatment started as soon as possible.

Your doctor is likely to watch for the development of signs and symptoms including:

  • Pain
  • Fatigue or weakness
  • Unintentional weight loss
  • Fever or night sweats
  • Headache, dizziness, nerve pain, or changes in vision or hearing
  • Bleeding
  • Anemia or other blood abnormalities
  • Swollen lymph nodes, liver or spleen
  • Heart and kidney problems


If you have osteoporosis, your doctor might recommend a medication (bisphosphonate) to increase bone density. Examples include alendronate (Binosto, Fosamax), risedronate (Actonel, Atelvia), ibandronate (Boniva) and zoledronic acid (Reclast, Zometa).

You can't control whether MGUS will lead to something more serious. But you can control many aspects of your health. Try to:

  • Stick to your checkup schedule. Diagnosing a serious condition, such as cancer, in the early stages may improve your treatment outcomes.
  • Follow a healthy lifestyle. You can reduce your risk of developing conditions unrelated to MGUS by eating a variety of fruits and vegetables, getting enough exercise and sleep, and reducing stress.

You may be referred to a doctor who specializes in blood disorders (hematologist).

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

What you can do

  • List any symptoms you're experiencing, including those that may seem unrelated to the reason you scheduled the appointment.
  • List key personal information, including any major stresses or recent life changes.
  • List all medications, vitamins or supplements you take, including doses.
  • 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.
  • List questions to ask your doctor.

For MGUS, some basic questions to ask your doctor include:

  • What kinds of tests do I need?
  • Do these tests require any special preparation?
  • How frequently do I need to schedule follow-up visits and testing?
  • Do you recommend any treatment or lifestyle changes?
  • I have other health conditions. How can I best manage these conditions together?

Don't hesitate to ask other questions you have.

What to expect from your doctor

Your doctor is likely to ask you a number of questions, including:

  • Do you have any numbness or tingling in your hands and feet?
  • Do you have osteoporosis?
  • Do you have a family history of MGUS?
  • Have you ever had a blood clot?
  • Have you ever experienced a broken bone?
  • Have you ever had cancer?
Last Updated: 07-29-2017
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