Monoclonal Gammopathy of Undetermined Significance (MGUS)

Overview

What is monoclonal gammopathy of undetermined significance (MGUS)?

Monoclonal gammopathy of undetermined significance (MGUS) is a blood disorder that affects plasma cells in your bone marrow. Most of the time, M proteins don’t cause issues and most people with MGUS don’t have symptoms. Healthcare providers often discover this condition after taking blood or urine samples as part of a routine physical examination. Rarely, this condition may also become a blood cancer or a more serious blood disorder. Providers typically do blood and urine tests every six to 12 months to look for signs that monoclonal gammopathy of undetermined significance is becoming a more serious medical problem.

Who does it affect?

Monoclonal gammopathy of undetermined significance is more common in people age 50 and older. Your risk of developing it increases as you age. Starting at age 50, people have a 3% to 5% chance of developing this condition. People age 75 and older have a 5% chance. You may be more likely to develop MGUS if you are:

  • Black.
  • Male and designated male at birth (DMAB).
  • Have a history of exposure to pesticides or insecticides.

How does this condition affect my body?

Monoclonal gammopathy of undetermined significance happens when your bone marrow produces abnormal plasma cells. Normally, individual plasma cells produce a specific type of antibody. Antibodies are special proteins that help identify and defend your body against germs.

In MGUS, abnormal plasma cells produce M proteins instead of antibodies. M proteins circulate in your bloodstream. These abnormal proteins may build up in your bloodstream and in your pee (urine), damaging your kidneys, heart and nerves. M proteins in your blood may also reduce your body’s ability to fight infection.

Is MGUS a cancer?

No, it’s not cancer but it can become cancer. Studies show that 20% of people with this condition develop multiple myeloma. Other people with monoclonal gammopathy of undetermined significance may develop other blood cancers or blood disorders:

Symptoms and Causes

What are the symptoms of monoclonal gammopathy of undetermined significance?

This condition rarely causes symptoms. When people have symptoms, they may include:

  • Tingling.
  • Weakness.
  • Numbness.

What causes the condition?

Healthcare providers aren’t sure why bone marrow produces abnormal plasma cells that then produce M proteins. The condition is linked to the following:

  • Genetic changes.
  • A history of autoimmune diseases.
  • A history of treatment for autoimmune diseases.
  • Exposure to high levels of radiation.
  • Exposure to pesticides and insecticides.

Diagnosis and Tests

How do healthcare providers diagnose monoclonal gammopathy of undetermined significance?

Providers analyze your blood and urine for signs of M protein. They also evaluate other factors to establish the risk MGUS will become cancer or a more serious blood disorder. These risk factors include:

  • The amount of M protein in your blood.
  • The type of M protein in your blood.
  • The amount of free light chains in your blood. Free light chains (FLC) are proteins made by plasma cells. FLC tests detect abnormal concentrations of free light chains.

Studies show that people who have all three risk factors have a 58% chance of developing blood cancer within 20 years. People who don’t have any risk factors have a 5% chance of developing blood cancer within 20 years.

Management and Treatment

How do healthcare providers treat monoclonal gammopathy of undetermined significance?

Most people with this condition don’t need treatment. While MGUS rarely becomes cancerous, your provider will monitor M protein levels in your blood and urine (pee) every six to 12 months for signs of cancer. Sometimes, people with this condition have an increased risk of bone loss or fracture. If you’re at risk, your provider may recommend medications and other steps to improve bone density.

Prevention

Can I prevent monoclonal gammopathy of undetermined significance?

No, you can’t prevent this condition. It happens when certain genes mutate, creating abnormal plasma cells that produce the abnormal proteins that cause MGUS symptoms.

Outlook / Prognosis

What can I expect if I have this condition?

In general, most people with monoclonal gammopathy of undetermined significance (MGUS) don’t have symptoms. A small percentage of people develop certain blood cancers or blood disorders. If blood and urine tests show M proteins, you’ll need blood and urine tests every six to 12 months. That way, your healthcare providers can watch for signs your condition is becoming a serious illness.

Living With

How do I take care of myself?

While providers don’t know what causes the condition, it’s been linked to autoimmune diseases and treatment for autoimmune diseases, as well as exposure to high levels of radiation, pesticides and insecticides. Monoclonal gammopathy of undetermined significance affects people age 50 and older. If you’re concerned about developing this condition, ask your healthcare provider about testing for the condition. If you have the condition, let your provider know if you develop symptoms such as numbness or tingling.

A note from Cleveland Clinic

Monoclonal gammopathy of undetermined significance (MGUS) is a bit of a medical mystery. As part of the condition’s name implies, there are things we don’t know. For example, healthcare providers don’t know why some people have the disease but never develop symptoms, while others develop blood cancer or more serious blood disorders. They are, however, working to unravel some of the mystery. For example, if you have this condition, providers may be able to predict if you’ll develop serious medical problems. If you’re concerned about the chance you may develop MGUS, ask your provider if potential risk factors apply in your situation. That information may help you decide if it makes sense for you to be screened for the condition.

Last reviewed by a Cleveland Clinic medical professional on 07/25/2022.

References

  • American Society of Clinical Oncology. Multiple Myeloma: Introduction. (https://www.cancer.net/cancer-types/multiple-myeloma/introduction) Accessed 7/25/2022.
  • International Myeloma Foundation: What Are MGUS, Smoldering and Active Myeloma? (https://www.myeloma.org/what-are-mgus-smm-mm) Accessed 7/25/2022.
  • Leukemia Foundation. Monoclonal Gammopathy of Undetermined Significance (MGUS). (http://www.leukaemia.org.au/blood-cancers/myeloma/mgus) Accessed 7/25/2022.
  • Leukemia & Lymphoma Society. Monoclonal Gammopathy of Undetermined Significance (MGUS) Facts. (https://www.lls.org/sites/default/files/file_assets/MGUS_FINAL.pdf) Accessed 7/25/2022.
  • Merck Manual Professional Version. Monoclonal Gammopathy of Undetermined Significance (MGUS). (http://www.merckmanuals.com/professional/hematology-and-oncology/plasma-cell-disorders/monoclonal-gammopathy-of-undetermined-significance-mgus) Accessed 7/25/2022.
  • National Cancer Institute. PDQ Adult Treatment Editorial Board. Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®): Patient Version. (https://www.ncbi.nlm.nih.gov/books/NBK66001/#_NBK66001_pubdet_) 2022 Jun 3. In: PDQ Cancer Information Summaries [Internet]. US. Accessed 7/25/2022.
  • National Organization for Rare Disorders. Monoclonal Gammopathy of Undetermined Significance. (https://rarediseases.org/gard-rare-disease/monoclonal-gammopathy-of-undetermined-significance/) Accessed 7/25/2022.

Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy