Monoclonal gammopathy of undetermined significance

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at July 1, 2016
StartDiseasesMonoclonal gammopathy of undetermined significance

Monoclonal gammopathy of undetermined significance (MGUS) occurs when the body produces large quantities of a paraprotein antibody. It is the most commonly diagnosed condition of the plasma cell dyscrasia spectrum of diseases. The disease is non-cancerous and occurs in roughly one percent of the general population under 70 years and in about three percent of people over 70 years who are in otherwise healthy condition.


Definition & Facts

Monoclonal gammopathy of undetermined significance is a disease in which the body creates an abnormal paraprotein called monoclonal protein or M protein. This paraprotein affects the immune system by altering plasma cells which are a type of white blood cell that produces antibodies in order to fight infections in the body.

The presence of paraproteins can be detected by testing the blood or urine. While monoclonal gammopathy of undetermined significance usually does not cause significant issues in most people, for some the disease can evolve over time into other diseases. These include some types of blood cancer

Symptoms & Complaints

Monoclonal gammopathy of undetermined significance does not typically present any symptoms. The presence of the disease is usually found when a patient is having a blood test or urine test performed for other medical reasons.

On rare occasions, patients may notice numbness in their hands and feet or may develop a rash that cannot be attributed to any other conditions. They may also experience trouble maintaining balance. This symptom is possibly due to damage caused to nerves by the buildup of the paraprotein in the blood.


The precise cause of monoclonal gammopathy of undetermined significance is unknown. It is known that at some point, the bodies of patients suffering from the disease begin to accumulate large quantities of the M paraprotein. It isn’t certain what triggers this buildup; however, genetic factors and environmental factors seem to have a part in sparking the process. As these paraproteins pile up, they crowd out the healthy cells located in bone marrow. This causes damage not only to the marrow, but also to other tissues throughout the body.

Diagnoses of monoclonal gammopathy of undetermined significance seem to be more common in those who have other diseases or conditions that weaken the immune system such as rheumatoid arthritis, HIV, and Crohn’s disease.

Other risk factors have to do with age, race, sex and family history. The average age of diagnosis for monoclonal gammopathy of undetermined significance is 70. African-Americans are diagnosed more often than other ethnicities. Cases are more common in men than women. Those with a family history of the disease are at a higher risk than those with no family history.

Diagnosis & Tests

Because monoclonal gammopathy of undetermined significance often gives the patient no symptoms, it is not usually found until the blood and urine are tested for other conditions. Once it is detected, the patient will usually be referred to a hematologist.

As a doctor specializing in blood disorders, they would be more familiar with a course of treatment over a general practitioner. The hematologist will begin by going over the medical history of the patient as well as performing a general physical examination of the patient. Then the doctor will order blood and urine tests.

The blood test will be used to determine a full blood count which checks the quantity of different types of blood cells. This tells the physician whether the bone marrow is working sufficiently or not. Another type of blood test called a serum protein electrophoresis may be ordered to measure the category and the number of paraprotein that is being produced by the plasma cells. The doctor may also order blood tests that will check the activity of the liver and kidneys and to determine levels of calcium in the body. Urine samples will also be checked for paraproteins.

Occasionally, a physician will utilize X-rays, CT scans, and bone marrow tests in order to rule out other, more serious conditions. X-rays allow the doctor to check different areas of bone for damage. CT scans can be used to see if the lymph nodes or organs such as the liver or the spleen are enlarged in the patient (hepatomegaly and splenomegaly, respectively).

When a bone marrow test is needed, a biopsy of the back of the hip bone is removed. This test is fairly simple and is usually performed as an outpatient procedure that takes less than a half-hour to complete. 

Treatment & Therapy

For most individuals afflicted with monoclonal gammopathy of undetermined significance, their overall health will not be affected and treatment will not be necessary. A small percentage may develop cancers of the plasma cells (myeloma) or cancers of the lymphatic system (lymphoma). The risk for all patients of the disease progressing is lifelong, making regular check-ups extremely important, especially in high-risk patients.

Physicians will typically check the blood of newly diagnosed patients every three or four months for the first year. They will be looking for a pattern in the level of paraproteins seen. If they remain at approximately the same amount, the doctor may reduce the number of blood tests performed each year. If the levels rise, blood tests may be ordered more often. About one percent of patients will develop complications.

Patients should contact their doctor immediately if they experience any of the following: a new pain in an area of the bone that does not subside, weight loss that cannot be explained, increasing difficulty in breathing, extreme fatigue, and a series of different types of infections that occur one after another. These infections are caused by the low white blood cell count the patient incurs.

Prevention & Prophylaxis

Because the triggers for the onset of monoclonal gammopathy of undetermined significance are not understood, there is little that can be done to prevent it occurring. Those that are diagnosed with the disease can reduce the risk of developing complications by pursuing regular checkups, living a healthy lifestyle, and keeping stress to a minimum.