Monoclonal gammopathy of uncertain significance (MGUS) (BSH 2009)


MGUS Definition – presence of a monoclonal protein in the serum or urine of an individual with no evidence of myeloma, AL amyloidosis, Waldenstrom’s or other related disorders.

M-protein Definition – monoclonal immunoglobulin secreted by an abnormally expanded clone of plasma cells in an amount that can be visualized by immunofixation of serum or urine.

Detectable in 1% of population overall


Lab tests

SFLC ratio can be used as a surrogate for secretion of monoclonal free light chains.

Ratio may be abnormal even when renal threshold for reabsorption of FLC has not been reached, meaning that monoclonal SFLC has not been detected on immunofixation of urine.


Causes for M-proteins


DDx – MGUS, Myeloma, SBP/SEP, AL Amyloidosis, Waldenstroms

Abnormal SFLC ratio can occur with any other immune dysregulation – e.g. SLE, HIV, HSCT


Of newly detected M-proteins:

- 72% MGUS, 19% Myeloma, 6% Other LPD, 2% Waldenstroms, 1% Amyloidosis


Diagnostic Criteria


 M-Proteins and Associated disorders


M-Protein Aggregation

  • Light chain cast nephropathy

  • AL Amyloidosis

  • Light-chain deposition disease

  • Adult Fanconi Syndrome

  • Type 1 Cryoglobulinaemia

M-Protein Antibody Activity

  • Cold agglutinins

  • Mixed Cryoglobulinaemia Type 2

  • Polyneuropathies


Prognosis of MGUS


Cumulative risk of progression to malignancy (MM or WM)

  • 10% at 10 years, 21% at 21 years, 26% at 25 years

  • i.e. risk does not change with time


Risk factors for malignant transformation include:

  • Type of M-protein – IgA and IgM higher risk than IgG

  • Level of M-protein – Transformation rate increases steadily with level of M-protein

  • Presence of an abnormal SFLC ratio


Patterns of disease progression vary

  • Stable from diagnosis then gradual or sudden rise

  • Gradual or sudden increase from diagnosis

  • Stable M-protein level but myeloma ROTI start to occur.


Who should be referred to clinic?


Those with:

  • IgD or IgE M-protein at any concentration

  • IgG M-protein >15g/l

  • IgA or IgM M-protein >10g/l

  • Significant BJP >500mg/l

Those with:

  • Symptoms suggesting Myeloma, LPD or amyloidosis

  • Asymptomatic but with unexplained abnormal investigations – calcium, creatinine etc


Remaining patients (the majority) can be monitored in the community 3-4 monthly for the first year and then 6-12 monthly long-term.

Patients should be educated about vigilance for symptoms of Myeloma / WM etc.