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Monoclonal gammopathy of undetermined significance

Essential points for quick revision.

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Paraprotein with acute organ injury

New renal failure, hypercalcaemia, cord symptoms, hyperviscosity, severe neuropathy, haemolysis, nephrotic syndrome or heart failure is not uncomplicated MGUS and requires urgent reclassification.

Action: Assess ABCDE, obtain FBC, calcium, renal, liver, SPEP, immunofixation, free light chains, urine and organ-specific tests, treat the acute syndrome and refer urgently to haematology, renal, neurology or cardiology for marrow, tissue and imaging rather than waiting for routine MGUS review.

Synopsis

Confirm MGUS without missing myeloma, lymphoma, amyloid or monoclonal gammopathy of clinical significance, stratify progression risk and provide proportionate monitoring with clear re-referral triggers.

  • MGUS is a diagnosis of exclusion: define the monoclonal isotype and burden, then show absence of a myeloma-defining event, lymphoma and protein-mediated organ disease.
  • Non-IgM MGUS usually has serum M-protein below 30 g/L, clonal marrow plasma cells below 10% and no attributable SLiM-CRAB event.
  • Light-chain MGUS has an abnormal free-light-chain ratio with raised involved light chain, no heavy-chain expression, marrow clonal plasma cells below 10% and urinary monoclonal protein below 500 mg/24 hours.

Key red flags

New bone pain, fracture, anaemia, hypercalcaemia, renal decline or recurrent infection raises active myeloma and requires repeat clonal and whole-body assessment.

Investigation priorities

01
First-line monoclonal studiesFirst stepFirst line

Confirm isotype, concentration and light-chain clonality.

Management branches

New monoclonal proteinConfirm clone and search for consequence

SPEP, immunofixation or free-light-chain testing detects possible monoclonality.

  1. Repeat or complete isotype, concentration, immunoglobulin and free-light-chain characterisation with FBC, renal, calcium, urine and symptom assessment.
  2. Escalate marrow, whole-body imaging, CT or tissue biopsy when burden, isotype, dynamic change or organ features warrant.
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Sources and review status3 sources · checked 27 Aug 2026 · clinical review pending
Sources

Sources and review status

National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.

Authoring stateRapid draftClinical stateAwaiting reviewJurisdictionUnited Kingdom