What Is Monoclonal Gammopathy of Undetermined Significance (MGUS)?

MGUS stands for monoclonal gammopathy of undetermined significance. It is a rare condition in which an abnormal protein is present in the blood. This abnormal protein is known as the “M” protein or monoclonal protein. This abnormal protein is produced by a certain type of plasma cell or white blood cell in your bone marrow. While Monoclonal gammopathy of undetermined significance or MGUS typically does not cause any problems, but sometimes over a period of time, it can progress to certain other disorders, including some types of blood cancer. So if you have MGUS, then it is necessary to keep getting regular checkups done so that any disease progression can be caught early on and treated at the earliest. Monoclonal gammopathy of undetermined significance or MGUS does not require any treatment if the disease does not progress.

Today we take a deeper look at what is monoclonal gammopathy of undetermined significance (MGUS) and try to understand it’s symptoms and what to do if the disease progresses.

What is Monoclonal Gammopathy of Undetermined Significance (MGUS)?

Monoclonal gammopathy of undetermined significance or MGUS is a condition that causes the production of an abnormal protein in the body. This protein is referred to as the “M” protein or monoclonal protein and it is manufactured by the white blood cells known as plasma cells. The “M” protein gets produced in the body’s bone marrow.(1)

Generally, Monoclonal gammopathy of undetermined significance or MGUS is not something you need to be concerned about, as it typically has no negative health effects. However, people who have MGUS are at a slightly higher risk of developing bone marrow and blood diseases. These can include serious forms of blood cancers, such as:

Sometimes, it might happen that the healthy cells in the bone marrow become crowded out once the body starts making a large amount of these abnormal “M” proteins. This is what can cause damage to the tissues throughout the body. Doctors usually only recommend regular monitoring of people who have Monoclonal gammopathy of undetermined significance or MGUS by undertaking regular blood tests. This is done to check for any signs of disease or cancer, which might develop in some cases of MGUS over a period of time.

Diagnosis of Monoclonal Gammopathy of Undetermined Significance (MGUS)

Patients suffering from Monoclonal Gammopathy of Undetermined Significance (MGUS) do not tend to have any typical symptoms of a disease. Many doctors end up finding “M” proteins in the blood of people having MGUS while they are testing for other diseases. Some people who have Monoclonal Gammopathy of Undetermined Significance may experience symptoms like numbness, rash or tingling throughout the body.

The presence of “M” proteins in blood or in the urine is also one symptom of Monoclonal Gammopathy of Undetermined Significance. It is also likely that other proteins in the blood might also be elevated when a person has MGUS. However, these could also be symptoms of some other medical conditions, such as hepatitis and dehydration.

In order to rule out any other medical condition or to determine whether Monoclonal Gammopathy of Undetermined Significance itself is causing the health problems, your doctor is likely to prescribe diagnostic tests, including:

24-hour Urine Protein Test: A 24-hour urine test is used to determine if the “M” protein is getting released in your urine. It also checks for kidney damage, which is one of the symptoms of a serious Monoclonal Gammopathy of Undetermined Significance related illness.

Detailed Blood Tests: Your doctor is going to prescribe a host of blood tests, such as a complete blood count (CBC), a serum calcium test, and a serum creatinine test. These tests will help check for any imbalances in the blood of the blood cells, a decrease in your kidney function, and high calcium levels. These signs are generally linked with serious MGUS-related diseases, such as multiple myeloma.

Imaging Tests: An MRI or a CT scan is ordered for checking the body for any bone abnormalities that are also associated with serious conditions related to Monoclonal gammopathy of undetermined significance or MGUS

Bone Marrow Biopsy: Your doctor will use a bone marrow biopsy to look for any signs of bone marrow cancers and other diseases linked with Monoclonal gammopathy of undetermined significance or MGUS. A bone biopsy is usually only performed when you experience symptoms of kidney failure, unexplained anemia, high calcium lesions or bone lesions.

Causes of Monoclonal Gammopathy of Undetermined Significance (MGUS)

Medical experts are not yet sure about what exactly causes Monoclonal gammopathy of undetermined significance or MGUS (5). It is believed that certain genetic, as well as environmental factors, have an effect on whether or not a person ends up having Monoclonal Gammopathy of Undetermined Significance.

However, what is known is that Monoclonal Gammopathy of Undetermined Significance causes the abnormal plasma cells in the bone marrow to start producing the “M” protein.

Progression of Monoclonal Gammopathy of Undetermined Significance (MGUS) Over Time

There are many people who have Monoclonal Gammopathy of Undetermined Significance (MGUS) who never experience any health issues related to the disease. However, there is about 1% of people with Monoclonal Gammopathy of Undetermined Significance who end up developing a more serious health issue each year. What type of condition you end up developing depends on the type of MGUS you have. There are three types of Monoclonal Gammopathy of Undetermined Significance (MGUS) and each one is associated with a greater risk of some specific health conditions. These include:

IgM MGUS: This type of Monoclonal Gammopathy of Undetermined Significance affects around 15 percent of people with MGUS. IgM Monoclonal Gammopathy of Undetermined Significance carries the risk of a rare type of cancer known as Waldenstrom macroglobulinemia, along with lymphoma, multiple myeloma, and AL amyloidosis.

Non-IgM MGUS: This type of Monoclonal Gammopathy of Undetermined Significance also includes IgG, IgD, or IgA MGUS. Non-IgM Monoclonal Gammopathy of Undetermined Significance affects the maximum number of people with MGUS and there is a great risk of non-IgM MGUS developing into multiple myeloma. In some people, though, non-IgM MGUS may also cause other serious disorders, such as light chain deposition disease or immunoglobulin light chain (AL) amyloidosis.

Light Chain MGUS (LC-MGUS): This is a newly classified type of Monoclonal Gammopathy of Undetermined Significance, which causes the “M” protein to be detected in your urine and is also known to lead to light chain multiple myeloma, light chain deposition disease or AL amyloidosis.

The conditions triggered by having Monoclonal Gammopathy of Undetermined Significance or MGUS can also cause health problems, such as blood clots, bone fractures, and even kidney problems over a period of time. These complications make it challenging to manage Monoclonal Gammopathy of Undetermined Significance and one has to treat all the associated diseases of MGUS as well.

Can Monoclonal Gammopathy of Undetermined Significance (MGUS) be Treated?

There is no treatment for Monoclonal Gammopathy of Undetermined Significance (MGUS).(5) This condition does not resolve on its own, but it also usually does not cause any symptoms or progress into a serious disease.(3)

Your doctor is going to recommend that you undergo regular blood tests and checkups, so that it is possible to keep a close eye on your overall health. Generally, these checkups will start within six months of being diagnosed with Monoclonal Gammopathy of Undetermined Significance. Apart from checking your blood for any changes in “M” proteins, your doctor will also search for any symptoms that could show that Monoclonal Gammopathy of Undetermined Significance is progressing. These symptoms include:

There is a high possibility that Monoclonal Gammopathy of Undetermined Significance (MGUS) can cause conditions that cause deterioration in bone mass(6), due to which a doctor may advise you to take medication for increasing your bone density if you are diagnosed with osteoporosis. Some of these medications that are prescribed include:

  • Binosto, Fosamax (alendronate).
  • Actonel, Atelvia (risedronate).
  • Boniva (ibandronate).
  • Zometa, Reclast (zoledronic acid).

Outlook for Monoclonal Gammopathy of Undetermined Significance (MGUS)

Most people who have Monoclonal Gammopathy of Undetermined Significance (MGUS) do not develop any type of serious bone marrow and blood conditions. However, it is always better to have your risk estimated by going for regular doctor visits and by getting regular blood tests done. Your doctor will also determine your risk of the disease progressing into another condition by taking the following into account:

Age of Diagnosis: The age at which you were diagnosed with Monoclonal Gammopathy of Undetermined Significance matters a lot. The longer you have had Monoclonal Gammopathy of Undetermined Significance, the greater are the chances of developing a serious illness.

Type, Size, and Count of “M” Proteins in your Blood: The more numerous and larger “M” proteins are in your blood, the greater the indication of developing serious diseases.

Level of Free Light Chains (another type of protein) in the Blood: Higher levels of these free light chain proteins are also a sign of progressing disease.

If you or any of your loved one is diagnosed with Monoclonal Gammopathy of Undetermined Significance or MGUS, then you need to follow your doctor’s monitoring plan for your condition. You need to stay on top of your MGUS so that you can minimize the risk of any future complications and also increase your likelihood of having a positive outcome if you develop any Monoclonal Gammopathy of Undetermined Significance associated disease.(4)

References:

  1. Kyle, R.A., 1995. 4Monoclonal gammopathy of undetermined significance (MGUS). Baillière’s clinical haematology, 8(4), pp.761-781.
  2. Zingone, A. and Kuehl, W.M., 2011, January. Pathogenesis of monoclonal gammopathy of undetermined significance and progression to multiple myeloma. In Seminars in hematology (Vol. 48, No. 1, pp. 4-12). WB Saunders.
  3. Go, R.S. and Rajkumar, S.V., 2018. How I manage monoclonal gammopathy of undetermined significance. Blood, 131(2), pp.163-173.
  4. Rajkumar, S.V., Kyle, R.A. and Buadi, F.K., 2010, October. Advances in the diagnosis, classification, risk stratification, and management of monoclonal gammopathy of undetermined significance: implications for recategorizing disease entities in the presence of evolving scientific evidence. In Mayo Clinic Proceedings (Vol. 85, No. 10, pp. 945-948). Elsevier.
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316455/
  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4268401/

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