Myelodysplastic Syndrome

Case Presentation:

In our morning report at WCH, we discussed a case of a patient presenting with chronic fatigue and macrocytic anemia. Subsequent assessment and investigations were consistent with a diagnosis of myelodysplastic syndrome (MDS).

Learning Points:

  1. Differential diagnosis of fatigue
  2. Differential diagnosis of macrocytosis
  3. Features of B12 and Folate Deficiency
  4. MDS: prognostication and basic management

Differential Diagnosis: Fatigue

Fatigue DDx

Differential Diagnosis:


B12 Deficiency:

B12 Def.png

  • physical exam findings include:
    • dementia/delirium/altered mental status
    • pallor/general anemia findings
    • Associated thyroiditis or vitiligo findings
    • Atrophic glossitis
    • Shuffling, broad-based gait with loss of vibration sense and positive Rhomberg (“hard to walk in a dark room”)
  • suggestive investigations include:
    • Macrocytic anemia and pancytopenia if severe
    • Blood film: hypersegmented neutrophils, megaloblasts
    • Low B12 levels with elevated MMA and homocysteine levels
      • MMA and homocysteine levels rise prior to fall of B12

Folate Deficiency:

Folate Def

  • no specific physical exam findings
  • deficiency in utero associated with fetal neural tube defects
  • supportive investigations include:
    • megaloblastic anemia
    • eleveated homocysteine but normal MMA
    • low RBC folate  (more stable measure of folate over several months)
    • low serum folate low (fluctuates; more reflective of recent intake)


Myelodysplastic Syndrome:

  • Key point in relation to this case: the presence of macrocytic anemia with a low reticulocyte count or a reticulocyte that is inappropriately normal in relation to the degree of the anemia indicates a possible underlying bone marrow problem.
  • MDS: Represent a spectrum of malignant stem cell disorders associated with abnormal cell development and risk of progression to leukemia
  • Presentation:
    • Typically a disease of elderly men
    • Asymptomatic with abnormalities in bloodwork/cytopenias
    • If symptomatic, may relate to one of the cytopenias
  • Diagnosis: relies on the findings on blood count, blood film, and bone marrow
    • cytogenetic analysis is important in characterizing MDS substypes
      • 5q variant confers a favourable prognosis and is associated with a specific therapy-lenalidomide; it is typically seen in females
  • Prognosis: risk of conversion to leukemia can be calculated using IPSS (International Prognosis Scoring System)
  • Management: depends on subtype, symptoms, and if refractory to transfusions. Hematology involvement is needed!

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