Alternative Names
Hematoporphyria; porphyrin disorder
Symptoms & Characteristics
Porphyrias are a group of at least 8 genetic conditions caused by problems in the chemical process that makes a substance called heme. Heme is primarily found in blood, liver and bone marrow, and is the part of hemoglobin that helps transports oxygen throughout the body.
There are two main forms of porphyrias, cutaneous porphyrias which affect the skin, and acute porphyrias which mostly affect the nervous system.
People who have cutaneous porphyrias may develop blisters, infections, scarring, pigment changes, itching, increased hair growth and swelling of their skin when it is exposed to sunlight. Cutaneous porphyrias include:
- Congenital erythropoietic porphyria
- Erythropoietic protoporphyria
- Hepatoerythropoietic porphyria
People who have acute porphyrias may have symptoms that include abdominal or chest pain, vomiting, diarrhea or constipation. During an attack, symptoms can also include muscle numbness, weakness, cramping or paralysis as well as seizures, fever, personality or mental changes. Attacks may develop over hours or days and may last for days or weeks. In rare cases, symptoms may be life-threatening. Acute porphyrias include:
- Acute intermittent porphyria
- ALAD (delta-aminolevulinate dehydratase) deficiency porphyria
Two other types of porphyria, hereditary coproporphyria and variegate porphyria involve a combination of skin and nervous system symptoms.
Additional symptoms of some types of porphyria may include: anemia enlargement of the spleen (spleenomegaly), abnormal liver function, and an increased risk to develop liver cancer. In some types of porphyria, people may only experience mild symptoms (or no symptoms at all) in their lifetime.
Treatment
Porphyria can be difficult to diagnose. However, early diagnosis, routine surveillance and treatment can help to manage some of the symptoms and sometimes prevent related problems. Treatment may include medications, heme supplementation, and blood drawing depending on type of porphyria.
How Common Is It?
The exact prevalence of porphyria is unknown, but probably ranges from 1 in 500 to 50,000 people worldwide.
Genetics & Inheritance
Although porphyria is typically genetic, many environmental factors strongly influence the occurrence and severity of symptoms in some types of porphyria. These factors may include alcohol, smoking, certain medications, hormones, sunlight exposure, certain illnesses, stress, and dieting or fasting.
People who have a separate genetic condition called hemochromatosis, are also at increased risk to develop porphyria cutanea tarda.
In addition to the genetic forms of porphyria, some cases are caused by non-genetic factors such as infections (like hepatitis C), iron overload, drinking alcohol, or exposure to certain medications. These cases are described as sporadic (or acquired) porphyria.
The genetic forms of porphyria are caused by mutations in different genes.
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Porphyria Genetics
|
| Form |
Type |
Gene |
Location* |
| Cutaneous porphyrias |
Congenital erythropoietic porphyria |
UROS |
10q25.2-q26.3 |
| Erythropoietic protoporphyria |
FECH |
18q21.3 |
| Hepatoerythropoietic porphyria |
UROD (2 mutations)** |
1p34 |
| Porphyria cutanea tarda*** |
UROD (1 mutation) |
1p34 |
| Acute porphyrias |
Acute intermittent p7gorphyria |
HMBS |
11q23.3 |
| ALAD deficiency porphyria |
ALAD |
9q34 |
| Other forms |
Hereditary coproporphyria |
CPO |
3q12 |
| Variegate porphyria |
PPOX |
1q22 |
|
*indicates chromosome number and gene location
**Although this is the same gene that causes porphyria cutanea tarda, these mutations tend to be unique to this type
***Only about 20% of cases are genetic, the remaining 80% are sporadic.
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We all have two copies of the genes that cause porphyria - one gene from each parent. The pattern of genetic inheritance varies by type.
- Acute intermittent porphyria, hereditary coproporphyria, porphyria cutanea tarda variegate porphyria, most cases of erythropoietic protoporphyria have autosomal dominant inheritance, which means that having a mutation in a single gene copy is sufficient to cause disease. An affected person has a 50% chance with each pregnancy to have an affected child.
- ALAD deficiency porphyria, congenital erythropoietic porphyria, hepatoerythropoietic porphyria, and rare cases of erythropoietic protoporphyria have autosomal recessive inheritance, which means that two mutations are necessary to cause disease, one from each parent. Both parents of an affected person are always both obligate carriers (each have only one mutation). Two carriers have a 25% chance with each pregnancy to have an affected child, but do not have symptoms themselves.
A genetic consultation with a trained genetic professional is important for a complete evaluation, accurate diagnosis, as well as discussion of the benefits and limitations of testing and recurrence risk.
Genetic Testing
Clinical genetic testing for porphyria can be broken down into two categories: diagnostic testing and carrier testing.
- Diagnostic testing may be used to confirm or rule out a diagnosis in a person suspected to have the disorder.
- Carrier testing for the autosomal recessive porphyria types is typically offered after a clinical diagnosis and/or mutations have already been identified in an affected family member(s).
Clinical genetic testing for some types of porphyria is available through an in person genetic consultation for people who are considered at risk. Use our find a genetic professional directory to locate a trained genetic professional in your area.
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