Gunther disease

Gunther disease
Classification and external resources
Hydroxymethylbilane, precursor to uroporphyrinogen III.
ICD-10	E80.0
ICD-9	277.1
OMIM	263700
DiseasesDB	3048
eMedicine	derm/145
MeSH	D017092

Gunther disease, also known as congenital erythropoietic porphyria (CEP), uroporphyrinogen III synthase deficiency and UROS deficiency,^[1][2] 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.^[3] It is a rare, autosomal recessive^[4] metabolic disorder affecting heme, caused by deficiency of the enzyme uroporphyrinogen cosynthetase.^[5] It is extremely rare, with a prevalence estimated at 1 in 1,000,000 or less.^[6] 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.^[7][8]

Causes

Gunther disease has an autosomal recessive pattern of inheritance.

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.^[4][9] The disorder is inherited in an autosomal recessive manner.^[4] 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 II 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.^[10][11]

Symptoms

There are many common symptoms that Gunther’s disease has on a patient’s display. The three main symptoms that are present in patients with this disease are (1) abdominal pain and cramping, which only occurs with certain types of the disease, (2) sensitivity to light that can causes rashes, scarring, and blistering, and (3) problems involving the nervous system and muscles that can produce seizures, mental disturbances, and damage to the nerves.^[12]
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.^[13] Scarring and skin discoloration is a potential result of this disease because the blisters are slow to heal. After an attack urine can become a reddish or brown color. Some attacks can cause life-threatening issues to arise, such as low blood pressure, extreme electrolyte imbalances and shock.^[12]
Some other symptoms can include muscle pain, numbness and/or tingling, paralysis, muscle weakness, soreness in legs or arms, backpain, and even some changes in personality.^[12]

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 all together. 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.^[14]
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.^[14]
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.^[14]
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.^[15] 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^[14]
Most doctors will tell all patients to refrain from consuming any alcohol, or drugs that could or will cause an attack. Doctors also advise patients to avoid any skin injuries and exposure to sun and use sunscreen whenever being exposed to the sun. It is usually beneficial to have a high carbohydrate diet^[12]

Complications and Expectations

There are many complications that can arise from having Gunther’s disease. Some of the most common are Coma, Gallstones, Paralysis, scarring skin, and respiratory failure.^[12]
Gunther’s Disease is a life-long disease and the symptoms are not consistent. There are forms that will produce fewer symptoms than others. If a patient takes the proper treatments and is consistent with avoiding the sun and any triggers it will help to increase the interval between attacks.^[12]

Epidemiology

There have been no registered cases of Gunther’s disease in the US. There are only 200 cases internationally and they have been reported in assorted areas. The life expectancy for a patient with Gunther’s disease is relatively high for the inadequate amounts of treatment for this disease. Most patients will live until adulthood around their 40’s or 60’s. There is no racial predilection and both females and males at equal rates have been found to acquire this disease. Gunther’s disease usually happens when the patient is a child or an infant, but it is not uncommon to have adult cases.^[14]

Eponym

The disorder is named after the German physician who discovered it, Hans Gunther (1884-1956).^[16]

See also

• Porphyria cutanea tarda
• List of cutaneous conditions
• List of dental abnormalities associated with cutaneous conditions

References

External links

• 1208352782 at GPnotebook
• Medical dictionary
• Porphyria, congenital erythropoietic at NIH's Office of Rare Diseases
• Rare Anemias Foundation