eMedicine Specialties > Dermatology > Metabolic Diseases

Congenital Erythropoietic Porphyria

Author: Jeanette L Hebel, MD, Department of Dermatology, Lancaster General Hospital
Coauthor(s): Maureen B Poh-Fitzpatrick, MD, Professor Emerita of Dermatology and Special Lecturer, Columbia University; Professor of Medicine (Dermatology), University of Tennessee
Contributor Information and Disclosures

Updated: Jan 12, 2009

Introduction

Background

Erythropoietic porphyria (EP) is a rare inborn error of porphyrin-heme synthesis inherited that is as an autosomal recessive trait. The inheritance of 2 mutant alleles for the gene encoding the enzyme uroporphyrinogen III synthase leads to accumulation of porphyrins of the isomer I type that are biologically useless but cause cutaneous photosensitivity characterized by blisters, erosions, and scarring of light-exposed skin.

Clinical manifestations can range from mild to severe. Chronic damage of skin, cartilage, and bones can cause mutilation. Hypertrichosis, erythrodontia, and reddish-colored urine are often present. Hemolytic anemia can be mild or severe, with resultant splenomegaly and osseous fragility.

The following is a selection of other eMedicine porphyria-related articles:

• Erythropoietic Protoporphyria
• Porphyria Cutanea Tarda
• Pseudoporphyria
• Variegate Porphyria

Pathophysiology

Erythropoietic porphyria is primarily a disorder of bone marrow heme synthesis. Deficient activity of the enzyme uroporphyrinogen III synthase in erythrocyte precursor cells causes a shift of the pathway away from the isomer III porphyrinogen production that can effect the end-product heme; isomer I porphyrinogens that cannot be used to form heme may be overproduced. The accumulated isomer I porphyrinogens are spontaneously oxidized to their corresponding porphyrins, which are water-soluble photosensitizers with a reddish hue.

These porphyrins are released from the maturing erythrocytes into the plasma and are excreted by renal mechanisms; urine with a port-wine color is produced. The interaction of excess porphyrins in the skin and light radiation causes photoxidative damage of biomolecular targets that is manifested as mechanical fragility and blistering that may result in severe scarring.

The hemolytic anemia of erythropoietic porphyria can cause hypersplenism in more serious cases. Hypertrophy of the bone marrow in such cases can lead to osseous fragility and pathologic fractures. Acral osteolysis and onycholysis may occur; bones and teeth are stained red by the deposition of porphyrin pigment. Ocular damage can lead to blindness. The photoactive nature of porphyrin molecules results in the bright pink fluorescence of these pigments in urine, teeth, and bones under Wood light illumination.

Frequency

United States

No registry for porphyrias exists in the United States; therefore, accurate data are lacking. Erythropoietic porphyria is rare.

International

Erythropoietic porphyria is reported in diverse populations. The total number of cases reported worldwide is less than 200.

Mortality/Morbidity

Remarkable clinical variability exists in erythropoietic porphyria. Despite the limited treatments that are currently available, the prognosis is not invariably poor. Most patients with erythropoietic porphyria survive into adulthood, with a life expectancy of 40-60 years.

Race

No racial predilection is reported for erythropoietic porphyria.

Sex

Erythropoietic porphyria occurs in both males and females with approximately equal frequencies.

Age

Erythropoietic porphyria typically occurs in infants or young children; however, several adult-onset cases are reported.

Clinical

History

The typical complaint is blistering and fragility of light-exposed skin in an individual with discolored urine. The presentation of erythropoietic porphyria at birth in a patient with a history of a difficult perinatal course and concomitant jaundice usually indicates severe disease. Patients may have a history of hemolytic anemia before the complete diagnosis was recognized. Very early prenatal expression with nonimmune hydrops fetalis has been reported.

Physical

Findings at physical examination may include the following:

• Skin
  • Photosensitivity, with formation of vesicles and bullae, occurs early in the course of the disease.
  • Increased fragility and erosions can contribute to mutilation, especially on the face (eg, nose, mouth, ears) and hands.
  • Hypertrichosis of the face and extremities is common.
• Oral
  • The teeth have a reddish color.
  • The teeth fluoresce under a Wood light due to porphyrin deposition in dentine and enamel.
• Urine
  • Pink staining of the diapers in the neonatal period is common.
  • This staining is due to the porphyrin pigment in the urine.
• Ocular¹
  • Ocular manifestations of erythropoietic porphyria include blepharitis, cicatricial ectropion, and conjunctivitis. Lagophthalmos is a major cause of light-induced ocular surface aggravation.
  • Scleral findings include interpalpebral fissures and pink fluorescence of the perilimbal sclera under a Wood light.
  • Subsequent bilateral corneal scarring may occur, with eventual blindness. The risk for malignant conjunctival degeneration is low.
• Skeletal
  • Porphyrins are also deposited in the bone, where they cause an orange-red fluorescence.
  • The severe loss of bone with subsequent contractures and deformities occurs in most adults with erythropoietic porphyria.
  • X-ray studies show osteopenia and acro-osteolysis.

Causes

Erythropoietic porphyria is caused by autosomal recessive inheritance of genes that encode abnormal uroporphyrinogen III synthase enzyme protein. The resultant deficient activity of this enzyme leads to hemolytic anemia, cutaneous photosensitivity, and their complications. The mutation that causes the most severe deficiency of the enzyme uroporphyrinogen III synthase is C73R.²

The GATA gene family, a group of transcription factors, has a crucial role in normal human hematopoiesis. A mutation in GATA1, an X-linked transcription factor, has been reported in association with erythropoietic porphyria.³

• Search for CME/CE on This Topic »

• Porphyria, Cutaneous (Pediatrics: General Medicine)
• Hydrops Fetalis (Pediatrics: Cardiac Disease and Critical Care Medicine)