Congenital Erythropoietic Porphyria (CEP) OR Gunther disease

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Other Names:Gunther disease, Uroporphyrinogen III synthase deficiency and UROS deficiency

Description:
Congenital  Erythropoietic  Porphyria  (CEP) is a congenital form of erythropoietic porphyria. The word porphyria originated from the Greek word porphura. Porphura actually means “purple pigment”, which, in suggestion, the color that the body fluid changes when a person has Gunther’s disease. It is a rare, autosomal recessive metabolic disorder affecting heme, caused by deficiency of the enzyme uroporphyrinogen cosynthetase. It is extremely rare, with a prevalence estimated at 1 in 1,000,000 or less. There have been times that prior to birth of a fetus, Gunther’s disease has been shown to lead to anemia. In milder cases patients have not presented any symptoms until they have reached adulthood. In Gunther’s disease, porphyrins are accumulated in the teeth and bones and an increased amount are seen in the plasma, bone marrow, feces, red blood cells, and urine.

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Symptoms:
Though expressivity is varied depending on the mutation responsible for decrease in enzyme function, severe cutaneous sensitivity is present in most cases of this Porphyria. An estimated 30–40% of cases are due to the C73R mutation, which decreases stability of the enzyme and results in <1% of its activity.

Usually, the disease shows itself soon after birth or in early childhood, but sometimes onset of disease is delayed until the teenage years or early adulthood.

*Red urine is usually the first sign noticed in newborn babies with CEP. The intensity of the redness can vary from day to day.

*The skin is very sensitive to light, especially direct sunlight, which may cause blisters or ulcers, which heal to leave scars. This most commonly happens at sun-exposed sites, for example the backs of the hands, the face, ears and scalp.

*The eyes may also be sensitive to bright sunlight or artificial light, which can cause ulcers and scarring. With time, some patients lose their eyelashes, making their eyes easily irritated by small particles of dust and fibre.

*The skin may take longer to heal after injury or blistering, and become infected.
Anaemia, which varies in severity, is common in CEP. Anaemia develops because porphyrin damages red blood cells, and causes tiredness, shortness of breath following minimal exertion, and paleness.

*The spleen, which removes the damaged red blood cells, can gradually become bigger and cause worsening of the anaemia and a reduction in the number of platelets (the blood cells that help to form blood clots to stop bleeding) and white cells (the blood cells that fight infections) in the blood. This can lead to an increased risk of bleeding (such as repeated nose bleeds) and infections.

CEP can occasionally cause thinning of the bones (osteoporosis), which can lead to bone fractures following minor injury.

Causes:
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. This means the defective gene is responsible for the disorder and is located on an autosome, and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder. When there is a homozygous mutation it causes a uroporphyrinogen III synthase and uroporphyrinogen cosynthase defect. When the enzyme uroporphyrinogen III synthase is reacting normally it results in the making of isomer III porphyrinogen, which is what is used to form heme. When isomer III porphyrinogen is not produced because of a poor production of uroporphyrinogen III synthase then isomer I porphyrinogen is made which will oxidize and give a reddish tint skin.

Diagnosis:
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.

Treatment:
There are a multiple ways to treat Gunther’s diseases, but one of the most crucial things that a person with this disease can do is limit themselves from sun exposure or eliminate sun exposure altogether. There are some sunscreens that have undesirable effects such as tropical sunscreens, but other sunscreens that have zinc oxide and titanium dioxide in them are shown to provide protection due to those light-reflective agents. To block the ultraviolet and visible light wavelengths and get the protection that patients with Gunther’s disease require, physical barriers are needed. It is also advised that patients wear protective clothing to block the sun from their skin. Plastic films can be attached to car windows and homes to filter out some of the wavelengths that could cause harm to someone’s skin suffering with this disease. Incandescent bulbs replace the normal fluorescent lamps. These bulbs release less light, which prevents the “porphyrin-exciting” wavelengths that fluorescent lights emit.

Other less beneficial treatments have been used to help treat Gunther’s disease. These include oral beta-carotene and other treatments such as activated charcoal and cholestyramine, which are used to interrupt and stop the porphyrins from being reabsorbed in the body. The reason that these oral treatments are unreasonable is because they require an extremely large dose of medicine and therefore are not beneficial.
Erythrocyte transfusions have been shown to be a successful measure in decreasing the appearance of the disease by trying to lower the erythropoiesis and circulating porphyrin levels. Unfortunately, having chronic erythrocyte transfusions, it can be extremely harmful to the body and can cause severe complications.

To help with dry eye symptoms and visual function, using topical lubrication can be used. A more invasive way to help treat Gunther’s disease would be to have surgery. There have been numerous studies that have stated that bone marrow transplantation is successful. This is a recently new development for Gunther’s disease so the long-term effects are still unresourced. If a patient has a life-threatening infectious complication then bone marrow transplantation is no longer relevant for them. There are also reports that stem cell transplantation is successful in a limited number of participants.

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.

Complications:
Photomutilation and transfusion dependent anemia are common complications. Liver disease is also observed in some cases. It has been reported that early childhood-onset haematological manifestations is a poor prognosis factor.

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.

Resources:
https://en.wikipedia.org/wiki/Gunther_disease
http://www.britishskinfoundation.org.uk/SkinInformation/AtoZofSkindisease/CongenitalErythropoieticPorphyria.aspx
http://www.porphyriafoundation.com/about-porphyria/types-of-porphyria/CEP

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