Monoclonal gammopathy of unknown significance (MGUS)

Protein = large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms
  • catalysing metabolic reactions
  • DNA replication
  • responding to stimuli
  • providing structure to cells and organisms
  • transporting molecules from one location to another
Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. [1]
Gamma globulin = globulins identified by their position after serum protein electrophoresis. The most significant gamma globulins are immunoglobulins (antibodies), although some immunoglobulins are not gamma globulins, and some gamma globulins are not immunoglobulins. [2]

Diagnosis

Diagnosis of monoclonal gammopathy of unknown significance (MGUS) is usually made after ordering a serum protein electropheresis (SPEP) (looking for myeloma, amyloidosis, complications of MGUS like neuropathy) based on signs or symptoms. Signs or symptoms that trigger an SPEP order:

  • fatigue or weakness 
  • Bone aches/pain*
  • lytic bone lesions,
  • bone fractures
  • Recurrent infections*
  • Paresthesia or numbness 
  • Carpal tunnel syndrome 
  • Spinal stenosis 
  • Biceps tendon rupture
  • Congestive heart failure with preserved ejection fraction
  • Increased bruising or bleeding
  • Orthostatic hypotension 
  • Voice changes 
  • Weight loss 
  • Macroglossia
  • Spontaneous periorbital purpura
  • Unexplained laboratory findings 
    • Elevated erythrocyte sedimentation rate
    • Elevated total protein level 
    • Anemia *
    • Renal insufficiency 
    • Hypercalcemia
    • Reduced anion gap 
    • Nephrotic syndrome
 *Common signs and symptoms that should raise concern about Waldenstrom's macroglobulinemia (WM) and multiple myeloma (MM) and should trigger a test for M-proteins. The assessment for M-proteins should not be the first testing undertaken reflexively for any of the aforementioned symptoms unless more common causes are first excluded. [3]

Prognosis

Low risk MGUS

Low risk = 0 of 3 risk factors for progression. Risk for progression is only 2% in these patients [3]

High risk MGUS

(from W Gonsalves, S Rajkumar. Monoclonal gammopathy of unknown significance. Ann Int Med. Dec 2022)

  • M-protein level >1.5 g/dL
  • non-IgG isotype
  • abnormal serum free light chain (sFLC) ratio

   Risk group   # risk factors Absolute progression risk  (%)   
           Overall    Account for death
    Low    0    5    2
Low-Intermed    1    21    10
    Intermed-high    2    37    18
    High    3    58    27

Monitor 

(from ] W Gonsalves, S Rajkumar. Monoclonal gammopathy of unknown significance. Ann Int Med. Dec 2022)
  • In 6 mos: complete blood count with differential, serum calcium test, serum creatinine test, SPEP with sIFE, and sFLC assay must be repeated. 
  • Every 1 to 3 months:   if there is an unexpected increase of at least 0.5 g/dL in the M-protein level and/or an increase of at least 10 mg/dL in the involved sFLC level, monitoring every 1-3 mos will allow determination of whether the patient is experiencing evolving M-protein changes consistent with an imminent progression to symptomatic MM or WM.
  • Every year: Lifelong yearly follow-up for assessment of the M-protein level is recommended for high risk MGUS 
  • Every 2-3 years: In patients with a low-risk MGUS profile whose repeated evaluation shows that they are stable, an assessment of the M-protein level can be repeated
  • If symptoms of progression develop: Assess M-protein level sooner 
  • Discontinue monitoring: routine follow-up can be discontinued in low-risk patients with MGUS who are older than 80 years or have a life expectancy of less than 5 years
  • every 1 to 3 months
  • Refer to hematology if not low risk

Contents

Diagnosis
Prognosis
Monitor

Glossary

  • Protein =molecues made of polypeptides
  • TIBC = Total iron binding capacity

ICD Codes

   Diagnosis Code    Link
Paraproteinemia

Multiple myeloma 
Waldenstrom's macroglobulinemia

References

[1] Proteins. Wikipedia
[2] Gamma globulins. Wikipedia
[3] W Gonsalves, S Rajkumar. Monoclonal gammopathy of unknown significance. Ann Int Med. Dec 2022