Congenital Erythropoietic Porphyria (CEP)

Congenital Erythropoietic Porphyria (CEP)This disease is extremely rare and is autosomal recessive. It is also known as Gunther's disease. The deficient enzyme is uroporphyrinogen III cosynthase (or uroporphyrinogen III synthase). Various mutations in the gene for this enzyme have been identified in different families. As is characteristic of the erythropoietic porphyrias, symptoms begin during infancy. Sometimes CEP is recognized as a cause of anemia in a fetus before birth. In less severe cases symptoms may begin during adult life. Porphyrins are markedly increased in bone marrow, red blood cells, plasma, urine and feces. Porphyrins are also deposited in the teeth and bones.


Skin photosensitivity may be extreme, and can lead to blistering, severe scarring and increased hair growth. Bacteria may infect the damaged skin. Facial features and fingers may be lost through phototoxic damage as well as infection. Red blood cells have a shortened life-span, and anemia often results. Synthesis of heme and hemoglobin are actually increased to compensate for the shortened red blood cell survival.

Treatment and Prognosis

Blood transfusions and perhaps removing the spleen may reduce porphyrin production by the bone marrow. Activated charcoal given by mouth is sometimes effective. Bone Marrow Transplantation has been very effective in some patients. Stem cell transplantation and gene therapy may also be an option in the future.


Additional reading about CEP:

Congenital Erythropoietic Porphyria


NORD gratefully acknowledges R.J. Desnick, PhD, MD, Professor and Chairman, and Dana O. Doheny, MS, CGC, Genetic Counselor, Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine of New York University; and Micheline M. Mathews-Roth, MD, Associate Professor of Medicine, Harvard Medical School, for assistance in the preparation of this report.

Synonyms of Congenital Erythropoietic Porphyria

  • CEP
  • Gunther disease
  • uroporphyrinogen III synthase deficiency
  • UROS deficiency

General Discussion

Congenital erythropoietic porphyria (CEP) is a very rare inherited metabolic disorder resulting from the deficient function of the enzyme uroporphyrinogen lll cosynthase (UROS), the fourth enzyme in the heme biosynthetic pathway. Due to the impaired function of this enzyme, excessive amounts of particular porphyrins accumulate, particularly in the bone marrow, plasma, red blood cells, urine, teeth, and bones. The major symptom of this disorder is hypersensitivity of the skin to sunlight and some types of artificial light, such as fluorescent lights (photosensitivity). After exposure to light, the photo-activated porphyrins in the skin cause bullae (blistering) and the fluid-filled sacs rupture, and the lesions often get infected. These infected lesions can lead to scarring, bone loss, and deformities. The hands, arms, and face are the most commonly affected areas. CEP is inherited as an autosomal recessive genetic disorder. Typically, there is no family history of the disease. Neither parent has symptoms of CEP, but each carries a defective gene that they can pass to their children. Affected offspring have two copies of the defective gene, one inherited from each parent.

CEP is one of a group of disorders known as the porphyrias. Each porphyria is characterized by abnormally high levels of particular chemicals (porphyrins) in the body due to deficiencies of certain enzymes in the step-wise synthesis of heme, the essential component of hemoglobin and various hemo-proteins. The porphyrias can be classified as cutaneous or acute depending on their respective manifestations (See There are eight major porphyrias. The symptoms associated with the various types of porphyria differ, depending upon the specific enzyme that is deficient. People who have one type of porphyria do not develop the other types, however, rare patients have had two different porphyrias.

Signs & Symptoms

The most common symptom of CEP is hypersensitivity of the skin to sunlight and some types of artificial light (photosensitivity), with blistering of the skin occurring after exposure. Affected individuals may also exhibit abnormal accumulations of body fluid under affected areas (edema) and/or persistent redness or inflammation of the skin (erythema). Affected areas of the skin may develop sac-like lesions (vesicles or bullae), scar, and/or become discolored (hyperpigmentation) if exposure to sunlight is prolonged. These affected areas of skin may become abnormally thick. In addition, in some cases, affected individuals may also exhibit malformations of the fingers and nails. The severity and degree of photosensitivity differ depending on the severity of the patient’s gene lesions which correlate with the deficient enzyme activity. Photosensitivity is seen from birth; however, in some cases, it may not occur until childhood, adolescence or adulthood. Patients also have erythrodontia, brownish discolored teeth, which fluoresce under ultraviolet light.

In more severe cases, other symptoms can include a low level of red blood cells (anemia), enlargement of the spleen, and increased hair growth (hypertrichosis). The anemia can be severe and such patients require periodic transformations to maintain sufficient red blood cells. In severely affected patients, anemia may be present in the fetus. Ocular problems also can occur including corneal scarring, eye inflammation, and infections.

Symptoms usually start in infancy or childhood and the diagnosis in most patients is suggested by the reddish color of the urine which stains the diapers. The diagnosis is made by finding increased levels of specific porphyrins in the urine. Diagnostic confirmation is made by measuring the specific (UROS) enzyme activity and/or by identifying the specific lesion(s) in the UROS gene which is/are responsible for the impaired enzyme.


Congenital erythropoietic porphyria is inherited as an autosomal recessive genetic condition. Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, and usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Mutations in the UROS gene cause CEP. The symptoms of CEP develop due to excessive levels of the specific porphyrins that accumulate in tissues of the body as a result of the markedly impaired function of the UROS enzyme.

Affected Populations

CEP is a very rare genetic disorder that affects males and females in equal numbers. Over 200 cases have been reported worldwide.

Related Disorders

Symptoms of the following disorders can be similar to those of CEP. Comparisons may be useful for a differential diagnosis:

CEP is one of a group of disorders known as the porphyrias. The porphyrias are all characterized by abnormally high levels of particular porphyrins in the body due to deficiencies of specific enzymes essential to the synthesis of heme for hemoglobin and other hemo-proteins. There are two major types of porphyria. The cutaneous porphyrias include CEP, erythropoietic protoporphyria, X-linked protoporphyria, and porphyria cutanea tarda. The acute porphyrias are characterized by the acute-onset of neurologic attacks (especially abdominal pain, hypertension, etc.) and include autosomal dominant acute intermittent porphyria, hereditary coproporphyria and variegate porphryia, the latter two acute porphyrias also may have cutaneous manifestations, and autosomal recessive aminolevulinate dehydratase deficient porphyria. The symptoms associated with the various types of porphyria differ, depending upon the specific enzyme that is deficient.

The erythropoietic protoporphyrias, including the autosomal recessive erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP), are rare cutaneous porphyrias due to deficiencies of the enzymes ferrochelatase (FECH) or aminolevulinate synthase 2, respectively. Due to abnormally low levels of these enzymes, excessive amounts of protoporphyrin accumulate in the bone marrow, blood plasma, and red blood cells. The major symptom of these disorders is hypersensitivity of the skin to sunlight and some types of artificial light, such as fluorescent lights (photosensitivity). However, they typically do not have the blistering lesions seen in CEP. After exposure to light, the skin may become itchy and red. Affected individuals may also experience a burning sensation on their skin. The hands, arms, and face are the most commonly affected areas. Some people with EPP/XLP may also have complications related to liver and gallbladder function. (For more information on these disorders, choose “erythropoietic protoporphyria” as your search term in the Rare Disease Database.)

There are several other types of porphyria, all of which involve deficiencies of specific enzymes. Most of the symptoms of these porphyrias are not similar to the symptoms found in CEP. However, individuals with porphyria cutanea tarda may develop skin lesions, and these lesions resemble the skin lesions found in CEP. It is important to note that individuals with one type of porphyria usually do not develop any of the other types, although rare patients have been reported to have inherited two porphyrias. In addition, there are skin disorders characterized by hypersensitivity to artificial light and sunlight besides CEP, such as epidermolysis bullosa. The skin lesions in these disorders do not resemble the skin lesions in CEP. (For more information on these disorders, choose “porphyria” and “epidermolysis bullosa” as your search terms in the Rare Disease Database.)


The diagnosis of CEP may be suspected when the reddish-colored urine is noted at birth or later in life. This finding, or the occurrence of skin blisters on sun or light exposure, should lead to a thorough clinical evaluation and specialized laboratory tests. The diagnosis can be made by testing the urine for increased levels of specific porphyrins. Diagnostic confirmation requires the demonstration of the specific UROS enzyme deficiency and/or the lesion(s) in the UROS gene.

Prenatal and preimplantation genetic diagnoses are available for subsequent pregnancies in CEP families.

Standard Therapies


Avoidance of sunlight is essential to prevent the skin lesions in individuals with CEP. The use of topical sunscreens, protective clothing, long sleeves, hats, gloves, and sunglasses are strongly recommended. Individuals with CEP will benefit from window tinting or using vinyls or films to cover the windows in their car or house. Before tinting or shading car windows, affected individuals should check with their local Registry of Motor Vehicles to ensure that such measures do not violate any local codes.

In addition to protection from sunlight, the anemia should be treated, if present. Chronic transfusions have been useful in decreasing the bone marrow production of the phototoxic porphyrins. When successful, bone marrow transplantation has cured patients with CEP, but is accompanied by specific risks of complications and demise. For more information on this treatment, contact the American Porphyria Foundation.

Referral to an expert porphyria center is recommended for expert diagnosis, care and genetic counseling – see Resources, The Porphyrias Consortium. Genetic counseling is strongly recommended. Other treatment is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010

For information about clinical trials sponsored by private sources, contact:

For information about clinical trials conducted in Europe, contact:

Porphyrin production in the bone marrow can be reduced by red blood cell (erythrocyte) transfusions but must be used with caution due to complications associated with chronic transfusion therapy.

Successful bone marrow transplantation has been curative for patients now over 10 years post-transplantation. Hematopoietic stem cell cord blood transplantation has also been successful.

The Rare Diseases Clinical Research Network (RDCRN), funded by the National Institute of Health (NIH) and the Office for Rare Diseases Research (ORDR), is sponsoring The Porphyrias Consortium, which will focus on the inborn errors of heme biosynthesis, the Porphyrias. It is bringing together senior porphyria experts at six academic institutions, the American Porphyria Foundation (APF), and industry to carry out clinical studies and clinical trials to accelerate the development of improved diagnosis and treatment for the patients with these rare diseases.

For more information:

The Porphyrias Consortium of the Rare Diseases Clinical Research Network

NORD Member Organizations

Other Organizations



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