What is Hepatoerythropoietic Porphyria (HEP)?
HEP is caused by low levels of the same enzyme that causes PCT, called uroporphyrinogen decarboxylase (UROD). In Familial PCT, there is only one mutated copy of the UROD gene, the other copy is normal. In HEP both copies of the UROD gene have mutations, one from the mother and one from the father. The symptoms of HEP resemble Congenital Erythropoietic Porphyria (CEP), with symptoms of skin blistering that usually begin in infancy or early childhood. HEP is a more severe form of PCT.
Skin photosensitivity (sun sensitivity) in HEP results in severe blistering and scarring. Increased hair growth (hypertrichosis) on sun-exposed skin, and reddish-colored urine due to the high levels of porphyrins are common.
HEP is caused by a deficiency of the enzyme uroporphyrinogen decarboxylase, due to the inheritance of mutations in both copies of a person’s URO-decarboxylase genes.
Who gets Hepatoerythropoietic Porphyria?
HEP is a very rare type of autosomal recessive porphyria. For a child to be affected, he/she must have received a mutated gene from each parent. This means each parent of an affected individual has Familial PCT, however, they may not know they have it since not all gene carriers develop symptoms.
How is Hepatoerythropoietic Porphyria diagnosed?
There are two types of testing; biochemical, meaning looking for “biomarkers” in the blood or urine, and genetic, meaning looking at the gene we know causes the disease directly from a blood sample.
Biochemical: To diagnose HEP the tests that need to be done are to measure the levels of total porphyrins in the urine or blood. These levels are generally very high in people with HEP.
Genetic: A blood sample is used to look at a person’s genes and by doing this it is possible to see if their genes have changes that can cause disease, called mutations. The gene that causes HEP is called UROD. Genetic testing is recommended for all patients even if they have a biochemical diagnosis.
Once the UROD mutations have been found, the patient’s immediate family members should be tested for the same mutations. This includes their parents, their siblings, and any children they may have. This will allow all family members to receive appropriate counseling even though many people with one mutation in the UROD gene will not have symptoms of Familial PCT.
What are treatments for Hepatoerythropoietic Porphyria?
The standard treatments for PCT: regularly scheduled phlebotomies (removal of certain amounts of blood), or low doses of hydroxychloroquine, are generally less effective in HEP but can still be attempted. The main way to manage symptoms is avoidance and/or protection from sunlight.
How is Hepatoerythropoietic Porphyria inherited?
HEP is an autosomal recessive condition. Autosomal means that the defect is not on the chromosomes that determine sex, and recessive means that patients who have HEP have inherited two mutated copies of the UROD gene, one from each of their parents. When someone with HEP has children, all their children will have Familial PCT since they will inherit one copy of the mutated UROD gene. The children will not necessarily develop symptoms of PCT but should be counseled accordingly.