Congenital erythropoietic porphyria
Other Names: Porphyria, congenital erythropoietic; CEP; Günther disease; Uroporphyrinogen III synthase, deficiency of; UROS deficiency; Congenital porphyria
Congenital erythropoietic porphyria (CEP) is the rarest type of porphyria and is commonly seen in infancy. It is characterized by severe skin photosensitivity that may lead to scarring, blistering, and increased hair growth at the face and back of the hands. Photosensitivity and infection may cause the loss of fingers and facial features.
Gunther disease is caused by mutations in the gene that encodes the enzyme uroporphyrinogen III synthase (UROS), located at human chromosome 10q25.2-q26.3
The disorder is inherited in an autosomal recessive manner.
Signs and symptoms
For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.
80%-99% of people have these symptoms
- Abnormal blistering of the skin(Blistering, generalized)
- Abnormal circulating porphyrin concentration
- Abnormal urinary color(Abnormal urinary colour)
- Abnormality of the foot (Abnormal feet morphology)
- Abnormality of the hand(Abnormal hands)
- Atypical scarring of skin(Atypical scarring)
- Cutaneous photosensitivity(Photosensitive skin)
- Hemolytic anemia
- Recurrent skin infections(Skin infections, recurrent)
- Splenomegaly(Increased spleen size)
30%-79% of people have these symptoms
- Immunodeficiency(Decreased immune function)
- Recurrent fractures(Increased fracture rate)
5%-29% of people have these symptoms
- Abnormality of skin pigmentation(Abnormal pigmentation)
- Blepharitis(Inflammation of eyelids)
- Ectropion(Eyelid turned out)
- Nonimmune hydrops fetalis
- Recurrent corneal erosions(Recurrent breakdown of clear protective layer of eye)
- Thickened skin(Thick skin)
- Thrombocytopenia(Low platelet count)
There are 4 steps in establishing the diagnosis of any porphyria. First, a thorough history (particularly family history) and physical exam are performed with special attention paid to sun-exposed skin. Biochemical measurements of porphyrins and precursors in the urine, feces, and blood are necessary.
Specialized labs are helpful in measuring activity of specific enzymes of the heme synthesis pathway and/or DNA and mutational analyses. In CEP, activity of uroporphyrinogen III synthase (the fourth enzyme in the heme biosynthetic pathway) will be markedly decreased.
In congenital erythropoietic porphyria, urine aminolavulanic acid and porphobilinogen are typically normal. However, uroporphyrin and coproporphyrin tend to be markedly elevated and moderately elevated, respectively, in the urine more than in the feces. Additionally, fecal protoporphyrin is typically mildly elevated.
In the red blood cells, uroporphyrin, coproporphyrin and protoporphyrin are all elevated, distinguishing this form of porphyria from the others. Finally, plasma analysis will demonstrate elevated uroporphyrin and coproporphyrin. Other nonspecific but helpful diagnostic clues are history of cutaneous photosensitivity, blistering, erosions, crusts and ulcerations leading to extensive scarring and deformation of the hands, loss of eyebrows, eyelashes with severe mutilation of cartilaginous structures like the nose, erythrodontia, and variable degree of hematologic involvement ranging from mild hemolytic anemia to intrauterine hydrops fetalis. Other early clues are red or violet staining of diapers.
Treatment for CEP may include a bone marrow transplant and hematopoietic stem cell cord blood transplantation. Blood transfusions or spleen removal may also reduce the amount of porphyrin produced by the bone marrow. Affected people must avoid sunlight exposure.
NIH genetic and rare disease info
Congenital erythropoietic porphyria is a rare disease.
Latest research - Congenital erythropoietic porphyria