Congenital Erythropoietic Porphyria
Congenital erythropoietic porphyria (CEP) is a very rare inherited metabolic disorder resulting from the deficient function of the enzyme uroporphyrinogen III synthase (UROS), the fourth enzyme in the heme biosynthetic pathway.
Other names of Congenital Erythropoietic Porphyria
Uroporphyrinogen III synthase deficiency
Causes of Congenital Erythropoietic Porphyria
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.
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.
In very rare cases, one particular mutation in another gene called GATA1 has been found to cause CEP.
So far, three CEP patients have been reported with the GATA1 mutation who do not have a mutation in the UROS gene.
Symptoms of Congenital Erythropoietic Porphyria
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.
Loss of sun exposed facial features such as lips, parts of the ears, and nose can also occur.
In addition, in some cases, affected individuals may also have loss of nails and end digits of the fingers due to infection of the underlying bone.
Diagnosis of Congenital Erythropoietic Porphyria
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 if the underlying genetic mutations are known.
Treatment of Congenital Erythropoietic Porphyria
Avoidance of sunlight is essential to prevent the skin lesions in individuals with CEP.
The use of topical, zinc- or titanium-oxide containing 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 home.
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, anemia should be treated if present.
Chronic blood transfusions have been useful in decreasing the bone marrow production of the phototoxic porphyrins but must be used with caution due to complications associated with chronic transfusion therapy.
When successful, bone marrow or hematopoietic stem cell transplantation can cure patients with CEP, but these procedures have a risk for complications and demise.