|Hydroxymethylbilane, precursor to uroporphyrinogen III.|
|Classification and external resources|
Gunther disease, also known as congenital erythropoietic porphyria (CEP), uroporphyrinogen III synthase deficiency and UROS deficiency, 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.
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. Exposure to long-wave ultraviolet light causes the affected skin to thicken and produce vesicles that are prone to rupture and infection; these secondary infections, along with bone resorption, can lead to disfigurement of the sun-exposed face and extremities. Enzyme dysfunction prevents the normal production of heme and hemolytic anemia is another common symptom, though a lack of hemolysis in this disease is possible. Porphyrins additionally accumulate in the bone and teeth, resulting in erythrodontia. When unexpected attacks occur, painful abdominal pain, as well as vomiting and constipation commonly follow the attacks. Exposure to the sunlight can cause discomfort and result in blistering, consciousness of heat, and swelling and redness of the skin.
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 uroporphyringen III synthase and uroporphyrinogen cosynthetase 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 uroporphyringen III synthase then isomer I porphyrinogen is made which will oxidize and give a reddish tint skin.
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Treatment and Management
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
Complications and Expectations
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.
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- Porphyria cutanea tarda
- List of cutaneous conditions
- List of dental abnormalities associated with cutaneous conditions
- Online Mendelian Inheritance in Man (OMIM) 263700
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