Porphyria

Porphyrias and Microcytic Anemia

• Overview: While porphyrias are primarily known for causing neurological and/or cutaneous symptoms due to the accumulation of porphyrin precursors, some types can also be associated with microcytic anemia
• Mechanism:
  • The underlying defect in heme synthesis can, in certain porphyrias, lead to a secondary disruption of iron metabolism and globin chain synthesis, contributing to microcytosis
  • This is not the primary mechanism, which is the build-up of toxic porphyrin precursors
• Which Porphyrias Can Be Associated with Microcytosis?
  • ALA Dehydratase Deficiency Porphyria (ADP): This is a very rare, autosomal recessive porphyria, and is the one most likely to have microcytic anemia. The buildup of ALA is toxic
  • Congenital Erythropoietic Porphyria (CEP): A rare, autosomal recessive erythropoietic porphyria, can sometimes present with microcytic features due to the overall disruption of erythropoiesis, though it is not the most common presentation
• Key Lab Findings to Consider Porphyria (in the context of Microcytic Anemia):
  • Unexplained Microcytic Anemia: If microcytosis is present but iron studies are normal and thalassemia has been ruled out, consider porphyria, especially if there are other suggestive symptoms
  • Photosensitivity: This is a key symptom that would point away from typical IDA, thalassemia, or ACD, and towards a porphyria
  • Neurological Symptoms: Acute porphyrias may manifest with abdominal pain, neurological issues (seizures, neuropathy), and psychiatric symptoms
  • Red or Dark Urine: While present in many conditions, this should also raise suspicion for a porphyria
  • Elevated Porphyrin Levels: Testing urine, stool, and blood for porphyrins and their precursors (ALA, PBG) is essential to confirm the diagnosis

How to Distinguish from Other Microcytic Anemias

• History and Symptoms: The presence of photosensitivity, neurological symptoms, or abdominal pain should raise suspicion for porphyria
• Porphyrin Studies: These are the key to diagnosis
  • Unlike IDA, iron studies will NOT show iron deficiency
  • Unlike thalassemia, hemoglobin electrophoresis will NOT show abnormal hemoglobins
• Family History: A family history of porphyria can be a clue

Adding to the Differential Diagnosis Table:

Here’s how we can expand the differential diagnosis table to incorporate Porphyrias:

Feature	Iron Deficiency Anemia (IDA)	Anemia of Chronic Disease (ACD)	Thalassemia	Sideroblastic Anemia	Porphyria (with Microcytosis)
MCV	Decreased	Decreased or Normal	Decreased	Decreased or Normal	Decreased
MCH	Decreased	Decreased or Normal	Decreased	Decreased or Normal	Decreased
RDW	Increased	Normal or Increased	Normal or Increased	Increased	Variable
Serum Iron	Decreased	Decreased	Normal or Increased	Increased	Normal
TIBC	Increased	Normal or Decreased	Normal	Decreased or Normal	Normal
Transferrin Saturation	Decreased	Normal or Decreased	Normal	Increased	Normal
Ferritin	Decreased	Normal or Increased	Normal	Increased	Normal
Peripheral Blood Smear	Pencil Cells	Mild abnormalities	Target Cells	Pappenheimer Bodies	Variable
Bone Marrow (if performed)	Decreased Iron Stores	Normal or Increased Iron Stores	Normal	Ringed Sideroblasts	Not always diagnostic
Hemoglobin Electrophoresis	Normal	Normal	Abnormal	Normal	Normal
Urine Porphyrins/Precursors	Normal	Normal	Normal	Normal	Often Elevated
Other Clues	Pica, etc.	Underlying disease	Family History	Drug Exposure	Photosensitivity, Neuro Sx

Key Points to Remember:

• While less common, porphyrias can sometimes present with microcytic anemia
• Always consider porphyria in the differential diagnosis of microcytic anemia if other common causes have been ruled out and there are suggestive clinical symptoms (photosensitivity, neurological issues, abdominal pain)
• Porphyrin studies are essential for diagnosis