National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Variegate porphyria


Other Names:
Porphyria variegate; VP; Porphyria, South African type; Porphyria variegate; VP; Porphyria, South African type; Protoporphyrinogen oxidase deficiency; PPOX deficiency See More
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Variegate porphyria (VP) is an inherited disorder that is caused by mutations in the PPOX gene that lead to the build-up of compounds normally involved in the body’s production of heme.[1][2] Heme is an important part of hemoglobin, the protein in blood that carries oxygen throughout our bodies. It is used in all the body’s organs. People with variegate porphyria have abnormal production of heme. They are very sensitive to sun exposure (photosensitive) and develop skin blisters and sores when they are exposed to sunlight. People with variegate porphyria can also have neurological symptoms in the form of episodes (acute attacks) of severe stomach pain, nausea and vomiting.[1][2] Symptoms usually begin in adulthood. Variegate porphyria is caused by mutations in the PPOX gene and is inherited in an autosomal dominant pattern.  Some people who have PPOX gene mutations never have symptoms of porphyria. People with variegate porphyria need to avoid sun exposure. Attacks are treated with medication and hospitalization. Attacks can be prevented by avoiding the factors that cause the symptoms.[1][2]
Last updated: 12/17/2018
Symptoms of variegate porphyria vary from person to person. This condition most often causes skin symptoms, neurological symptoms, or both. The symptoms usually start in adulthood. Skin symptoms are related to sun sensitivity and people with variegate porphyria may develop blisters, sores and discoloration after sun exposure.[1][2] Neurological symptoms are related to acute attacks which may occur after exposure to certain medications, hormonal changes, dieting, or alcohol. For some people, the exact cause for an attack may not be known. During an acute attack of variegate porphyria, a person may experience abdominal pain, nausea, vomiting, constipation, and diarrhea. Muscle weakness, seizures, and increased heart rate and blood pressure may also occur.  Mental changes such as anxiety and hallucinations have been reported as being part of an acute attack, but these are no longer considered part of this condition.[3]. Attacks vary in length from a few days to weeks. After an attack, most of the symptoms go away fairly quickly. Some symptoms, such as muscle weakness may take months to get better. 

Hepatocelluar carcinoma has been reported as a rare complication of variegate porphyria.[2] This is a type of cancer that starts in the liver. In addition, people with variegate porphyria are at increased risk to develop kidney disease.[2][3] 

Last updated: 12/17/2018

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 22 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Hypopigmented skin patches
Patchy loss of skin color
0001053
Scarring 0100699
Thin skin 0000963
30%-79% of people have these symptoms
Abnormal blistering of the skin
Blistering, generalized
Blisters
[ more ] 		0008066
Cutaneous photosensitivity
Photosensitive skin
Photosensitive skin rashes
Photosensitivity
Sensitivity to sunlight
Skin photosensitivity
Sun sensitivity
[ more ] 		0000992
5%-29% of people have these symptoms
Abdominal pain
Pain in stomach
Stomach pain
[ more ] 		0002027
Anxiety
Excessive, persistent worry and fear
0000739
Confusion
Disorientation
Easily confused
Mental disorientation
[ more ] 		0001289
Constipation 0002019
Depressivity
Depression
0000716
Motor polyneuropathy 0007178
Muscle weakness
Muscular weakness
0001324
Nausea and vomiting 0002017
Seizure 0001250
Visual hallucinations 0002367
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance 0000006
Paralysis
Inability to move
0003470
Peripheral neuropathy 0009830
Porphyrinuria 0010473
Psychosis 0000709
Tachycardia
Fast heart rate
Heart racing
Racing heart
[ more ] 		0001649
Vomiting
Throwing up
0002013
Showing of 22 |
Last updated: 7/1/2020
Variegate porphyria is caused by mutations in the PPOX gene.[4] The PPOX gene is responsible for making an enzyme known as protoporphyrinogen oxidase. Mutations in PPOX reduce the activity of that enzyme and this allows compounds called porphyrin precursors to build up in the body. These compounds are formed during the normal process of heme production, but reduced activity of protoporphyrinogen oxidase allows them to accumulate to toxic levels. The acute attacks seen in variegate porphyria can be brought on by a number of different factors, including certain medications, hormonal changes in the body, alcohol, dieting and other factors that have not been identified.[1][4]
Last updated: 12/17/2018
Variegate porphyria is inherited in an autosomal dominant manner, which means one copy of the PPOX gene in each cell is mutated.[1][4] All individuals inherit two copies of each gene. In autosomal dominant conditions, an individual has a disease-causing mutation in only one copy of the gene that causes the person to have the disease. The mutation can be inherited from either parent. There is nothing either parent can do, before or during a pregnancy, to cause a child to have this.

Each child of an individual with variegate porphyria has a 50% or 1 in 2 chance of inheriting the mutation.Offspring who inherit the PPOX mutation may be more or less severely affected than their parent. This single mutation reduces the activity of an enzyme needed for heme production, which increases the risk of developing signs and symptoms of porphyria.Not all people who inherit a PPOX gene mutation will develop the symptoms of variegate porphyria.[4]
Last updated: 12/17/2018
The diagnosis of variegate porphyria is suspected based on the clinical findings. Once a person is suspected of having variegate porphyria, additional testing including urine, stool and blood tests are done. The diagnosis of variegate porphyria is made by finding an excess of the compounds, coproporphyrin in urine and both coproporphyrin and protoporphyrin in stool.[2][3][4] The most sensitive screening test is a plasma porphyrin assay.[3] Genetic testing of PPOX gene can be used to confirm the diagnosis as well, and can be helpful for telling the difference between different types of porphyria.
Last updated: 12/17/2018

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Hospitalization is often necessary for acute attacks to help manage the pain and other neurological symptoms. Medications for pain, nausea and vomiting, and close observation are generally required. Mild attacks may be managed by giving the person a large amount of glucose or other carbohydrates. More severe attacks are treated with hemin, an injection of the heme protein, to help stop the attack. The response to heme therapy is best if started early in an attack. Heme must be administered by vein (intravenously). Panhematin® is the only commercially available heme therapy for treatment and prevention of acute porphyria attacks in the United States. Heme arginate, which is marketed in some other countries, is another type of heme.[2][4]

Attacks can also be avoided by avoiding the ‘trigger’ for the attack. The trigger can be different for different people. Triggers include certain medications, alcohol, dieting, and hormonal changes in the body. Sometimes, however, the trigger is unknown. Avoiding excess sun exposure can reduce the blisters and skin lesions.[4]

Last updated: 12/17/2018

Management Guidelines

  • Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.  
  • The American Porphyria Foundation offers a document that includes information about porphyria, types, testing, and treatment with Panhematin®.  Click the "document" link above to view these guidelines.
The long term outlook for people with variegate porphyria varies with the severity of the symptoms. With early diagnosis and treatment, variegate porphyria is rarely life threatening and it doesn’t usually get worse with time.  People with this condition are at increased risk for liver cancer and kidney disease.[3][5]
Last updated: 12/17/2018

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include acute intermittent porphyria and, particularly, porphyria cutanea tarda (see these terms). The presence of a fluorometric peak (626-628 nm) in plasma is pathognomonic and allows a definitive diagnosis of variegate porphyria rather than porphyria cutanea tarda.
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Social Networking Websites

  • RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

Organizations Providing General Support

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources

  • The HealthWell Foundation provides financial assistance for underinsured patients living with chronic and life-altering conditions. They offer help with drug copayments, deductibles, and health insurance premiums for patients with specific diseases. The disease fund status can change over time, so you may need to check back if funds are not currently available.

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Variegate porphyria. This website is maintained by the National Library of Medicine.
  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
  • The National Digestive Diseases Information Clearinghouse (NIDDK) offers information on this condition. Click on the link to view information on this topic.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Variegate porphyria. Click on the link to view a sample search on this topic.

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  1. Porphyria. Genetics Home Reference (GHR). July, 2009; https://ghr.nlm.nih.gov/condition/porphyria.
  2. Variegate Porphyria. National Organization for Rare Disorders (NORD). Updated 2017; https://rarediseases.org/rare-diseases/variegate-porphyria/.
  3. Hift RJ, Peters TJ, Meissner PN. A review of the clinical presentation, natural history and inheritance of variegate porphyria: its implausibility as the source of the “Royal Malady”. J Clin Path. Mar 2012; 65(3):200-205. https://www.ncib.nlm.nih.gov/pubmed/22049218.
  4. Singal AK, Anderson KR. Variegate Porphyria. GeneReviews. Feb 2013; https://www.ncbi.nlm.nih.gov/books/NBK121283/.
  5. Porphyria Variegata. Orphanet. Feb 2009; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=79473.