What are the other Names for this Condition? (Also known as/Synonyms)
- EPP (Erythropoietic Protoporphyria)
What is Erythropoietic Protoporphyria? (Definition/Background Information)
- Porphyrias are disorders resulting from excess porphyrin buildup in the liver and bone marrow. Manufacturing hemoglobin and related proteins (heme synthesis) involves a class of molecules, called porphyrins. Porphyrias are either inherited or acquired, and are described as acute, chronic, and cutaneous
- Erythropoietic Protoporphyria (EPP) is a form of cutaneous porphyria that manifests mainly as a skin condition. In this condition, the skin is severely sensitive to light, which often presents as scarring, blistering, and hair growth on the hands/face
- Erythropoietic Protoporphyria is a genetic condition that is inherited in most cases. However, rarely, cases of acquired EPP have been documented. The onset of symptoms usually occurs in childhood, especially around puberty
- A healthcare provider typically diagnoses this genetic disorder by testing blood and feces of the affected individual for porphyrin compounds and gene mutations
- The treatments for Erythropoietic Protoporphyria includes the application of topical sunscreens and other measures to protect oneself from direct sunlight exposure. In case the liver is severely affected by cirrhosis or hepatic fibrosis, a liver transplant may be necessary
- The prognosis of Erythropoietic Protoporphyria is determined by the severity of symptoms and extent of liver damage. In many individuals, the prognosis is good with accurate diagnosis and early treatment
Who gets Erythropoietic Protoporphyria? (Age and Sex Distribution)
- Erythropoietic Protoporphyria is an uncommon form of porphyria affecting 1 in 75,000 to 1 in 200,000 individuals globally
- In most cases, symptoms are seen during childhood; while severe forms of EPP have symptom-onset in infancy. In many children, the symptoms occur at the time of puberty, which may be related to hormonal influences during puberty
- Some individuals may have the genetic mutations, but present no symptoms, due to which the condition can remain underdiagnosed
- EPP affects males slightly more than females, though both genders are affected
- The disorder occurs without racial or ethnic bias
What are the Risk Factors for Erythropoietic Protoporphyria? (Predisposing Factors)
- A family history of Erythropoietic Protoporphyria increases the risk of a newborn being diagnosed with the condition
It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.
Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.
What are the Causes of Erythropoietic Protoporphyria? (Etiology)
Erythropoietic Protoporphyria is caused by certain gene mutations, which are involved in the production of “heme”. In many cases, the FECH gene on the long arm of chromosome 18 is involved.
- Heme is a critical component of iron-containing proteins called hemoproteins. Hemoglobin is one such protein, which is the oxygen carrier in blood. Blood, bone marrow, and liver have the most heme protein in them
- Most of the EPP cases develop as an autosomal dominant and some as an autosomal recessive condition; a family history may be observed. Occasionally, this type of porphyria may be acquired and a few cases have been reported
- Mutations in the defective gene affects porphyrin metabolism. A compromised porphyrin metabolism causes a buildup of porphyrins in the body
- The enzyme involved in end heme synthesis, called ferrochelatase, is dysfunctional or deficient. Due to this, large amounts of protoporphyrins aggregate in the red blood cells (RBCs) of the bone marrow
- But, since this compound is not miscible in water, unlike in other forms of porphyrias, it is not removed from the body through urine. Thus, the level of PBG and porphyrin compounds in urine remains normal
- However, it can be excreted in feces and feces remains concentrated with these secretions. The abnormal and excess accumulation in the RBCs, consequently increase the load on liver, due to which the liver is severely affected
- It is important to note that the symptoms of the condition are observed, when the level of the enzyme drops below 30%. Since, in a majority of cases the enzyme level stays above 70%, many individuals do not have significant symptoms of the disorder
Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.
Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).
What are the Signs and Symptoms of Erythropoietic Protoporphyria?
The signs and symptoms of Erythropoietic Protoporphyria due to porphyrin buildup are mostly related to the skin due to photosensitivity (on exposure to sunlight). The severity of the symptoms may vary vastly from one individual to another.
The skin signs and symptoms of EPP may include:
- Skin gets inflamed with burning sensation
- Blistering of the skin; formation of sacs (vesicles) on the skin
- Recurrent skin infections
- Abnormal scarring of the skin
- Hyperpigmentation and hypopigmentation (change in skin pigmentation)
- Sun-exposed areas of the body are affected the most, such as the face, neck, shoulders, arms (including the wrists and fingers), chest and back
- Weak and fragile skin that is easily broken on minor trauma or injury
- Over time, thickening of skin
- Increased hair growth or hirsutism; hypertrichosis (or abnormal hair growth)
- In many cases, even exposure for a few minutes, or exposure to sunlight through glass windows/curtain wall panels, or ultraviolet light from equipment can trigger skin symptoms
- Ultraviolet light from behind a welder’s mask can also result in skin symptoms
- During pregnancy and menstruation, the level of protoporphyrins in blood cells are believed to decrease, and so, the degree of light-sensitivity is noted to reduce
Other signs and symptoms of EPP may include:
- Abnormal color of urine (reddish)
- Inflammation of the liver is commonly noted
- Hemolytic anemia (destruction of red blood cells)
- Splenomegaly (spleen enlargement)
How is Erythropoietic Protoporphyria Diagnosed?
The diagnosis of Erythropoietic Protoporphyria is made by the following tools:
- A complete physical examination and an assessment of symptoms
- An evaluation of the affected individual’s full medical history
- Measurement of the porphyrin levels in blood or feces: Excess amounts of porphyrin compounds (uroporphyrins) are produced, and therefore, seen in feces and blood
- Measurement of ferrochelatase enzyme activity
- Molecular genetic testing before or after birth, to confirm FECH gene mutation(s); i.e., mutations in the “heme” gene
- Liver biopsy to determine the extent of liver damage: A biopsy is performed and sent to a laboratory for a pathological examination. The pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis
Note: Testing for urine levels of porphyrin compounds are generally inconclusive, since the compound is insoluble in water, and urine levels do not reflect increased body levels of porphyrin compounds.
Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.
What are the possible Complications of Erythropoietic Protoporphyria?
The potential complications of Erythropoietic Protoporphyria may include:
- Severe deformation of the skin
- Anemia and other conditions, due to low levels of oxygen transport
- Severe emotional stress due to cosmetic concerns
- Bacterial infections following characteristic blistering of the skin
- Vitamin D and mineral iron deficiency
- Increased protoporphyrins in bile can result in gall bladder stones formation
- Gallstones can block bile duct resulting in acute and chronic cholecystitis
- Chronic liver conditions, such as scarring and fibrosis, due to liver toxicity
How is Erythropoietic Protoporphyria Treated?
The treatment measures of Erythropoietic Protoporphyria may include:
- Avoiding direct exposure to sunlight and the application of beta-carotene topical sunscreen creams
- Vitamin A analogues which makes the skin less sensitive to sun’s rays
- Medications to help the liver eliminate protoporphyrins may be given. Undertaking treatment for liver disorders; in some cases, a partial or complete liver transplant may be necessary
- Treating iron and vitamin D deficiencies by taking suitable supplements
- In some individuals, estrogen medications may be beneficial
- To treat increased bile quantity of protoporphyrins, activated charcoal and bile acid sequestrants (group of resins to bind bile, such as cholestyramine) are used
- If the levels of protoporphyrin in blood is high, plasmapheresis may be helpful in some cases
How can Erythropoietic Protoporphyria be Prevented?
- Currently, there are no specific methods or guidelines to prevent Erythropoietic Protoporphyria, since it is a genetic condition
- Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
- If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
- Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Erythropoietic Protoporphyria
Regular medical screening at periodic intervals with tests and physical examinations are highly recommended.
What is the Prognosis of Erythropoietic Protoporphyria? (Outcomes/Resolutions)
- The prognosis of Erythropoietic Protoporphyria varies with the severity of the condition. It is assessed on a case-by-case basis
- In most cases, the symptoms of EPP are not severe and they may be controlled through proper treatment. Therefore, the prognosis is good in many individuals
Additional and Relevant Useful Information for Erythropoietic Protoporphyria:
The other forms of cutaneous porphyria include X-linked dominant protoporphyria (XLDPP), congenital erythropoietic porphyria (CEP), porphyria cutanea tarda (PCT), hereditary coproporphyria (HCP), and variegate porphyria (VP).