Congenital Erythropoietic Porphyria (CEP)

Congenital Erythropoietic Porphyria (CEP)

Congenital erythropoietic porphyria, or CEP, is an extremely rare, inherited metabolic disorder. It is caused by genetic defects which lead to deficiency of the enzyme uroporphyrinogen III cosynthase (UROS). The disease is characterised by extreme photosensitivity (abnormal cutaneous reaction to sunlight) which can leave severe scarring, blister formation and the loss of digits or other features. Damaged skin can become infected, leading to further necrosis and deformities. The face, hands and arms are the most significantly affected as they are frequently exposed; sometimes presenting as severe disfiguration.


The incidence of CEP is not known, but it is exceedingly rare; as of 2006, there were approximately 150 cases reported worldwide. Onset is usually during the early years of life as the genetic defects are present from birth. A milder form with onset in adulthood has been described in a small number of patients; six individuals as of 1990.


Congenital erythropoietic porphryia belongs to a family of diseases known as porphyrias. These are characterised by the overproduction and accumulation of chemicals, known as porphyrins, in various tissues within the body. The porphyrias come about due to faults or deficiencies in the pathway which leads to the production of haem (a major component of the haemoglobin in red blood cells).

CEP is caused by a genetic defect, or mutation, in the UROS gene. This gene encodes an enzyme, uroporphyrinogen III cosynthase, which is essential to the step-wise progression of haem synthesis (see Figure 1). The effect of the mutation is that the enzyme is only marginally active. This means that not only is haem synthesis severely impeded, but also that the pathway takes an alternative route, leading to the build of porphyrins. In the case of CEP, the particular porphyrins in excess are uroporphyrin I and coproporphyrin I.
Haem Biosynthetic pathway

 Figure 1. The Haem Biosynthetic Pathway, illustrating the defect in CEP

Figure 1. The Haem Biosynthetic Pathway, illustrating the defect in CEP

While the enzyme’s activity is dramatically reduced in CEP patients, it is not entirely absent as this would likely result in the complete absence of red blood cells and therefore death. The porphyrins are partially excreted in the urine and faeces, though a large portion enters into circulation and is deposited in bodily tissues; primarily the bone marrow, skin, blood and teeth. Porphyrin accumulation has toxic effects on the cells in these organs. This accounts for many of the symptoms experienced by CEP patients, including their heightened photosensitivity.

CEP’s rarity is partially due to its pattern of inheritance as a recessive trait. This means that an individual needs to have two copies of the defective gene – one from their mother and one from their father – in order for the condition to be present. An individual with just one defective gene will be a carrier of the disease but will not exhibit any symptoms, since the properly functioning gene is able to produce intermediate levels of the enzyme. There is typically no family history of CEP and both parents are healthy.

A number of mutations in the UROS gene have been discovered in CEP patients, all cause dysfunction of the UROS enzyme. Of the 35 described, the C73R mutation is the most common, present in about a third of all cases. This particular mutation is associated with a severe form of the disease.


Symptoms of CEP are diverse and can range from mild to severe. Along with cutaneous damage due to enhanced photosensitivity, CEP patients commonly suffer anaemia due to the breakdown of red blood cells (hemolysis). The following symptoms may be present to differing extents in individual patients:


  • Blistering and rashes on light-exposed skin
  • Scarring
  • Increased skin fragility
  • Skin destruction and erosion
  • Abnormal hair growth (hypertrichosis/hirsutism)
  • Loss of eyebrows and eyelashes
  • Mutilation of cartilage structures, such as the ears and nose
  • Loss of digits and facial features
  • Bacterial infection of damaged skin, possibly leading to further necrosis and deformation

Blood and other tissues

  • Anaemia due to the breakdown of red blood cells
  • Excessive red blood cell production (erythrocyte hyperplasia)
  • Bone loss, fragility or hardening
  • Enlarged spleen (splenomegaly)
  • Brown, pink or red discolouration in urine, due to the presence of porphyrins
  • Teeth stained red (erythrodontia), also due to accumulation of porphyrins
  • Ocular (eye) lesions


  • Brownish colour to the amniotic fluid
  • Accumulation of fluid in the fetus whilst still in utero (hydrops fetalis)

In addition to the physical symptoms, CEP patients often suffer poor mental health. This is due to both the level of pain and discomfort experienced and the psychological impacts of their appearance. These individuals can be stigmatised and often avoid interaction with other people. Many struggle both socially and professionally, thus CEP has an extreme impact upon patient quality of life.


CEP is the only porphyria that can be diagnosed prenatally. It is indicated by raised levels of uroporphyrin I in the amniotic fluid as early as 16 weeks in utero. More commonly, diagnosis is in infancy or childhood through a combination of the following methods:

  • History of patient symptoms
  • Quantitative screening using spectrophotometry or fluorimetry is considered the most accurate method of diagnosis. When uroporphyrin I and coporphyrin I are present in blood a plasma spectrofluorimetry is seen at 615-620 nm.
  • Measurement of elevated levels of uroporphyrin I and coproporphyrin I in blood, urine or faecal analyses
  • Examination of the eyes or urine using a Wood’s lamp


Total avoidance of sunlight and other sources of visible/UV light (i.e. solariums) is vital to preventing skin damage in CEP. Sun-protective clothing and sunscreen containing the light-blocking compounds zinc oxide or titanium dioxide may offer some protection. Plastic window films and window tinting around the home and in the car can reduce damaging wavelengths of light penetrating the skin. In addition, incandescent light bulbs emit less phototoxic wavelengths of light than fluorescent lights. Physicians recommend CEP patients try to avoid physical injury which may worsen fragile or damaged skin.

CEP treatments can be radical and patient response is varied:
Bone marrow transplantation (BMT) – the only therapy to date that presents a potential cure for CEP. It has proved extremely successful in a handful of patients, however the long-term results of BMT are not yet known. This form of therapy also comes with significant risks, including infectious complications and a high mortality rate. In a few children, BMT has resulted in complete remission of CEP. Improvements included normal haemoglobin, considerably reduced uroporphyrin I in the urine and no skin lesions in spite of unrestricted sun exposure; this is evidence of the best case scenario. Stem cell cord blood transplantation has also been reported effective in a few CEP patients.

Blood transfusions – these decrease the production of red blood cells and hence porphyrins in CEP patients. Transfusions have successfully reduced disease symptoms in several patients, however there are complications associated with chronic transfusions (i.e. iron overload).

Splenectomy – a splenectomy is the surgical removal of the spleen. It can increase the lifespan of red blood cells, reducing anaemia.

Oral sorbent medications – these include activated charcoal and cholestyramine which act by binding the excess porphyrins and preventing their absorption. In several patients these have reduced porphyrins in the blood and urine, in one case leading to complete remission. In contrast, there are also several reports of no effect and one of exacerbated condition; thus, caution should be exercised. Further, this treatment may be accompanied by the mild complication of poor nutrient absorption.

Oral beta-carotene – may act as a mild photoprotectant to reduce the symptoms of photosensitivity, though treatment usually requires unreasonably large doses. It has been trialed in CEP with minimal efficacy.

Oxygen quenchers – these are oral medications, such as ascorbic acid and alpha-tocopherol, which mop up excess reactive oxygen species to lessen porphyrin-induced photodamage; also only marginally effective.


The prognosis for a CEP patient depends on both the clinical severity of the condition and their response to available treatment. Severity is mainly dependent on the amount of residual activity the UROS enzyme has. Into the future, potential therapies may exist in the form of stem cell transplantation and gene therapy to correct the mutation and produce a functional UROS enzyme.

During puberty, a child’s haemoglobin levels increase to that of an adult. Along with an increase in haem comes a rise in porphyrin levels in CEP patients, therefore increase in symptoms or relapse may occur during adolescence. Where treatment is ineffective, the life expectancy of CEP patients is shortened.


  • American Porphyria Foundation, n.d, Congenital Erythropoietic Porphyria (CEP), accessed 23rd August 2010, <>.
  • Canadian Association for Porphyria, n.d, Congenital Erythropoietic Porphyria, accessed 23rd August 2010, (no longer online).
  • Hebel, J.L, 2009, Congenital Erythropoietic Porphyria: Treatment & Medication, eMedicine Specialties, accessed 23rd August 2010, <>.
  • Hift, R.J, Meissner, P.N & Kirsch, R.E, 1993, ‘The effect of oral activated charcoal on the course of congenital erythropoietic porphyria’, The British Journal of Dermatology, 129(1):14-17.
  • National Organization for Rare Disorders, 2008, Porphyria, Congenital Erythropoietic, accessed 22nd December 2015,<>.
  • Singh, D.K & Rai, R, 2008, ‘Congenital Erythropoietic Porphyria’, Indian Pediatrics, 45:865.
  • Wiederholt, T, 2006, ‘Identification of mutations in the uroporphyrinogen III cosynthase gene in German patients with congenital erythropoietic porphyria’, Physiological Research, 55(suppl. 2):S85-S92.