Porphyrias are a group of metabolic disorders caused by a disturbance in the synthesis of heme. In most cases, porphyria is caused by a hereditary enzyme defect. The disease patterns differ depending on the affected enzyme, and the variants of porphyria can be clinically differentiated between acute and nonacute forms. Patients with porphyria present with photosensitive skin eruptions and sometimes systemic symptoms such as abdominal pain and neuropathy. Porphyrias are managed by avoiding triggers, such as sun exposure and consumption of alcohol. When flares occur, therapy is targeted toward symptomatic relief.

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Definition and Epidemiology


Porphyrias are rare metabolic disorders caused by impairments in heme synthesis.

  • Characterized by a buildup of substances called porphyrins
  • Types of porphyria are differentiated by the type of porphyrin that accumulates in the blood, urine, or stool.
  • May affect the skin, liver, and nervous system


  • Incidence: approximately 5 cases per 100,000 population
  • Most common type is porphyria cutanea tarda (PCT).
  • 2nd most common type is acute intermittent porphyria.


Porphyrias are due to enzymatic defects in heme biosynthesis:

  • Heme is produced in the liver and bone marrow.
  • Involves 8 enzymatic steps, starting with glycine
  • Enzyme absence or dysfunction leads to buildup of heme precursors.
  • Excess precursors accumulate in tissues, leading to clinical symptoms.
Table: Porphyrias and their associated defective enzyme
Form of porphyria Defective enzyme
Porphyria cutanea tarda Uroporphyrinogen III decarboxylase
Acute intermittent porphyria Porphobilinogen deaminase
X-linked protoporphyria δ-Aminolevulinic acid synthase 2
Congenital erythropoietic porphyria Uroporphyrinogen III synthase
Hereditary coproporphyria Coproporphyrinogen oxidase
Variegate porphyria Protoporphyrinogen oxidase
Erythropoietic protoporphyria Ferrochelatase

Most commonly, porphyrias are due to an inherited enzyme defect within the heme biosynthesis pathway. They may rarely be acquired later in life:

  • Alcohol abuse
  • Infections (e.g., hepatitis C and HIV/AIDS)
  • Increased estrogen levels

Clinical Presentation

Clinical presentation depends on the pattern of organ involvement.

  • Chronic porphyria → increased skin manifestations (e.g., blisters and erosions)
  • Acute porphyria → systemic findings (e.g., abdominal pain, liver enzyme elevation)
  • Most common forms:
    • Porphyria cutanea tarda
    • Acute intermittent porphyria 
    • Erythropoietic protoporphyria:
      • Congenital erythropoietic porphyria (autosomal recessive)
      • Erythropoietic protoporphyria (autosomal dominant)

Porphyria cutanea tarda

  • Most common porphyria
  • Caused by defect in uroporphyrinogen III decarboxylase
  • Can be inherited in an autosomal dominant manner or acquired later in life
  • Acquired PCT can be triggered by:
    • Alcohol abuse
    • Exogenous estrogens
    • Infection (often hepatitis C)
  • Leads to buildup of uroporphyrinogen III
  • Symptoms include:
    • Photosensitivity of skin
    • Blistering skin lesions
    • Scars on face and back of hands
    • Hypertrichosis
    • Hyperpigmentation
  • Porphyrin deposits cause progressive liver damage:
    • Elevated liver function enzymes
    • Liver nodules can be detected on ultrasound.
  • Patients will have dark-colored urine due to elevated uroporphyrins.
Erosions, crust, and blisters are evident on the hands of this patient with pct

Erosions, crust, and blisters are evident on the hands of this patient with porphyria cutanea tarda.

Image: “Erosions, crust, and blisters are evident on the hands of this patient with porphyria cutanea tarda” by Department of Internal Medicine, Minia University, Minia, Egypt. License: CC BY 2.5

Acute intermittent porphyria

  • 2nd most common porphyria
  • Peak incidence: 3rd decade of life
  • Porphobilinogen deaminase is the affected enzyme. Increase in preceding intermediates in metabolic pathway:
    • Porphobilinogen (PBG)
    • δ-Aminolevulinic acid (ALA)
  • Symptoms include:
    • Colicky abdominal pain
    • Neurologic abnormalities
    • Disorientation

Congenital erythropoietic porphyria

  • Caused by defect in uroporphyrinogen III synthase
  • Symptoms include:
    • Skin photosensitivity: blister formation
    • Erythrodontia (red teeth)
    • Colicky abdominal pain
Erythrodontia in congenital erythropoietic porphyria

Photograph showing the presence of lesions and scars on both hands of a patient with congenital erythropoietic porphyria

Image: “Erythrodontia in congenital erythropoietic porphyria” by Department of Oral Pathology and Microbiology, Kamineni Institute of Dental Sciences, Narketpalli, Andhra Pradesh, India. License: CC BY 2.0


The diagnosis of porphyrias is typically made using specialized blood tests.

  • If suspected, can screen with urine and blood tests:
    • Urine would have elevated PBG levels.
      • PBG is 1 of the 1st substances in the porphyrin synthesis pathway.
      • Other urinary porphyrins may also be elevated.
    • Serum porphyrins will be elevated.
  • Discolored urine when left standing (yellow to dark red)
  • PBG also detected in stool
  • To confirm diagnosis, test for function of suspected enzyme defect.


There is no known cure for porphyria.

  • Prevent flares with strict avoidance of triggers (e.g., alcohol, sunlight).
  • Symptomatic treatment when flares occur:
    • Phlebotomy to remove porphyrins
    • Pain management → NSAIDs, opioids
    • Vomiting → antiemetics
    • Tachycardia → beta-blockers
    • Seizures → antiepileptics
  • Acute attack: IV hemin → decreases heme biosynthesis

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Differential Diagnosis

  • Lead poisoning: leads to decreased hemoglobin synthesis. Symptoms of lead poisoning include nausea, vomiting, headaches, encephalopathy, and peripheral neuropathy. Treatment is aimed at decreasing lead levels with chelation.
  • Acute anemia: condition in which individuals have low hemoglobin levels. Symptoms include fatigue, shortness of breath, pallor, and weakness. Anemia may occur because of blood loss, decreased RBC production such as in iron deficiency, or increased RBC destruction such as in hemolysis. Management is aimed at improving hemoglobin levels and treating the underlying conditions.
  • Hepatitis B and C: viral infections of the liver that cause inflammation and damage of hepatocytes. The presentation of these 2 infections depends on whether the infection is acute or chronic, and it is specific to the type of hepatitis present. Diagnosis is established by detecting antibodies or viral antigens in the serum. 
  • Hodgkin lymphoma: malignancy of B lymphocytes originating in lymph nodes. The disease presents most commonly with lymphadenopathy (neck most commonly involved), night sweats, weight loss, fever, and at times, splenomegaly and hepatomegaly. Hodgkin lymphoma is managed with chemotherapy and radiotherapy.
  • Acute lymphoblastic leukemia (ALL): hematologic malignancy that starts in the bone marrow. Patients present with fatigue, pallor, bleeding, fever, and infection related to the anemia, thrombocytopenia, and lack of functional WBCs seen in acute leukemia. Diagnosis is made with peripheral blood smear and bone marrow biopsy findings.


  1. Bissell, D. M., Anderson, K. E., Bonkovsky, H. L. (2017). Porphyria. New England Journal of Medicine 377:862–872. https://www.nejm.org/doi/10.1056/NEJMc1712682
  2. Gounden V, Jialal I. (2020). Acute porphyria. In: StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK537352/
  3. Gounden V, Jialal I. Acute porphyria. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK537352/

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