Table 3.

Disorders to Consider in the Differential Diagnosis of Congenital Erythropoietic Porphyria

Disease NameGene(s)MOIClinical Features
OverlappingDistinguishing
Porphyria cutanea tarda (PCT) type I (OMIM 176090)See footnote 1.
  • Cutaneous photosensitivity w/blistering & friability of skin in sun-exposed areas
  • Facial hypertrichosis
  • Discolored urine
  • Usually manifests in adulthood
  • Distinct biochemical porphyrin profile
Porphyria cutanea tarda (PCT) type II UROD AD
Hepato-erythropoietic porphyria UROD AR
  • Phenotype similar to PCT
  • Manifests in early childhood
  • Discolored urine
  • Photosensitivity
  • Distinct biochemical porphyrin profile
  • Developmental delay (in some)
Hereditary coproporphyria CPOX AD20% of affected persons experience photosensitivity w/skin blistering in sun-exposed areas.
  • Acute (hepatic) porphyria
  • Acute attacks of abdominal or generalized pain; can be assoc w/neurologic symptoms
  • Incompletely penetrant in absence of environmental inducers
  • Usually manifests after puberty
Variegate porphyria PPOX AD
Myeloid malignancyElderly adults w/myelodysplastic syndrome may exhibit features of CEP. 2, 3
Epidermolysis bullosa simplex (EBS) KRT5
KRT14 		AD 4
  • Fragility of skin → nonscarring blisters caused by little/no trauma
  • Major & minor subtypes share common feature of blistering above dermal-epidermal junction at the ultrastructural level.
Junctional epidermolysis bullosa (JEB) LAMA3
LAMB3
LAMC2
COL17A1 		AR
  • Fragility of skin & mucous membranes, manifest by blistering w/little or no trauma
  • Herlitz JEB (classic severe form): blisters present at birth or become apparent in neonatal period
  • Non-Herlitz JEB: may be mild w/blistering localized to hands, feet, knees, elbows
Dystrophic epidermolysis bullosa COL7A1 AR
  • Blisters affecting whole body may be present in neonatal period.
  • Oral involvement
  • Corneal erosions
  • Esophageal erosions
  • Severe nutritional deficiency & secondary problems
  • "Mitten" hands & feet
  • >90% lifetime risk of aggressive squamous cell carcinoma
ADBlistering, often mild & limited to hands, feet, knees, elbows; heals w/scarringDystrophic nails possibly the only manifestation
1.

80% of persons with porphyria cutanea tarda (PCT) have type I PCT (also referred to as acquired or "sporadic" PCT because it is not known to be associated with an inherited genetic alteration). Type I PCT is characterized by normal URO-decarboxylase activity systemically when affected individuals are asymptomatic. Inhibition of the enzyme activity resulting in PCT can be caused by excessive alcohol intake, hemochromatosis, viral hepatitis (mostly hepatitis C), HIV infection, certain medications, and environmental exposures such as aromatic polyhalogenated hepatotoxins. Treatment consists of eliminating or treating the underlying cause and, if symptoms persist, frequent phlebotomies or therapy with oral low-dose hydroxychloroquine.

2.
3.

Affected individuals had normal erythrocyte URO-synthase activity. Presumably, the CEP-like manifestations resulted from genetic or functional changes associated with the bone marrow disorder.

4.

EBS caused by pathogenic variants in KRT5 or KRT14 is usually inherited in an autosomal dominant manner; in rare families, especially those with consanguinity, it can be inherited in an autosomal recessive manner.

From: Congenital Erythropoietic Porphyria

Cover of GeneReviews®
GeneReviews® [Internet].
Adam MP, Feldman J, Mirzaa GM, et al., editors.
Seattle (WA): University of Washington, Seattle; 1993-2024.
Copyright © 1993-2024, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2024 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.