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

Differential Diagnosis:

B12 Deficiency:

• 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:

• 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!