Variegate porphyria

Title

Other Names:

Porphyria variegate; VP; Porphyria, South African type; Porphyria variegate; VP; Porphyria, South African type; Protoporphyrinogen oxidase deficiency; PPOX deficiency See More

Categories:

Congenital and Genetic Diseases; Kidney and Urinary Diseases; Metabolic disorders; Congenital and Genetic Diseases; Kidney and Urinary Diseases; Metabolic disorders; Nervous System Diseases; RDCRN; Skin Diseases See More

This disease is grouped under:

Porphyria

Summary Summary

Variegate porphyria (VP) causes the abnormal production of heme, an important part of the protein in blood that carries oxygen throughout our bodies. It is used in all the body’s organs. Symptoms of VP usually begin in adulthood and are different from person to person. Symptoms may include sun sensitivity and the development of skin blisters and sores when exposed to sunlight. Some people with VP have episodes (acute attacks) of severe stomach pain, nausea, and vomiting. In some cases, muscle weakness, anxiety, and seizures may occur. Variegate porphyria is caused by genetic changes in the PPOX gene and is inherited in an autosomal dominant pattern. Some people who have PPOX gene variants never have symptoms of porphyria. Diagnosis of VP is based on the symptoms, clinical examination, and other blood and urine tests. The diagnosis may be confirmed by the results of genetic testing. Treatment of VP is focused on managing the symptoms. People with VP are usually advised to avoid sun exposure and factors that can cause attacks. Attacks can be treated with medication and hospitalization.^[1]^[2]^[3]

Last updated: 4/2/2021

Symptoms Symptoms

The following list includes the most common signs and symptoms in people with variegate porphyria. These features may be different from person to person. Some people may have more symptoms than others, and they can range from mild to severe. This list does not include every symptom that has been described in variegate porphyria.

Symptoms of variegate porphyria can include:

Blisters and sores on sun exposed skin
Darkened or lightened skin patches
Stomach pain
Nausea and vomiting
Constipation
Muscle weakness
Seizures
Mental changes

The symptoms usually start in adulthood. Skin symptoms are related to sun sensitivity. Other symptoms occur during acute attacks. Attacks can last from a few days to weeks. After an attack, most of the symptoms usually go away fairly quickly. Some symptoms, such as muscle weakness may take months to get better. Without treatment, neurological symptoms and mental changes may occur. With early diagnosis and treatment, variegate porphyria is doesn’t usually get worse with time. People with this condition may be at increased risk for liver cancer and kidney disease.^[1]^[2]^[3]

Last updated: 4/2/2021

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.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Abdominal pain	Pain in stomach Stomach pain [ more ]	0002027
Abnormal circulating porphyrin concentration		0010472
Increased urinary porphobilinogen		0012217
Porphyrinuria		0010473
30%-79% of people have these symptoms
Abnormal blistering of the skin	Blistering, generalized Blisters [ more ]	0008066
Anxiety	Excessive, persistent worry and fear	0000739
Back pain		0003418
Chest pain		0100749
Constipation		0002019
Cutaneous photosensitivity	Photosensitive skin Photosensitive skin rashes Photosensitivity Sensitivity to sunlight Skin photosensitivity Sun sensitivity [ more ]	0000992
Elevated urinary delta-aminolevulinic acid		0003163
Motor polyneuropathy		0007178
Proximal muscle weakness in upper limbs		0008997
Skin erosion		0200041
Skin vesicle		0200037
Tetraparesis		0002273
5%-29% of people have these symptoms
Abnormal autonomic nervous system physiology		0012332
Elevated hepatic transaminase	High liver enzymes	0002910
Hyperpigmentation of the skin	Patchy darkened skin	0000953
Hyperreflexia	Increased reflexes	0001347
Hypertension		0000822
Hypertrichosis		0000998
Hyponatremia	Low blood sodium levels	0002902
Hypopigmentation of the skin	Patchy lightened skin	0001010
Hyporeflexia	Decreased reflex response Decreased reflexes [ more ]	0001265
Ileus		0002595
Inappropriate antidiuretic hormone secretion		0031218
Milia	Milk spot	0001056
Nausea		0002018
Neurogenic bladder	Lack of bladder control due to nervous system injury	0000011
Respiratory paralysis		0002203
Scarring		0100699
Seizure		0001250
Sensory impairment		0003474
Tachycardia	Fast heart rate Heart racing Racing heart [ more ]	0001649
Thickened skin	Thick skin	0001072
1%-4% of people have these symptoms
Anemia	Low number of red blood cells or hemoglobin	0001903
Chronic kidney disease		0012622
Coma		0001259
Hallucinations	Hallucination Sensory hallucination [ more ]	0000738
Hepatocellular carcinoma		0001402
Paranoia		0011999
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance		0000006
Paralysis	Inability to move	0003470
Peripheral neuropathy		0009830
Psychosis		0000709
Vomiting	Throwing up	0002013

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 2/1/2021

Do you have updated information on this disease? We want to hear from you.

Cause Cause

Variegate porphyria occurs when the PPOX gene is not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all. Not everyone who has a PPOX variant will have symptoms of variegate porphyria.^[1]

Last updated: 4/2/2021

Inheritance Inheritance

Variegate porphyria is inherited in an autosomal dominant pattern. All individuals inherit two copies of each gene. Autosomal means the gene is found on one of the numbered chromosomes found in both sexes. Dominant means that only one pathogenic variant on one copy of a gene is necessary to have the condition. The variant can be inherited from either parent. Sometimes an autosomal dominant condition occurs because of a new genetic variant (de novo) and there is no history of this condition in the family.

Each child of an individual with an autosomal dominant condition has a 50% or 1 in 2 chance of inheriting the variant and the condition. Typically, children who inherit a dominant variant will have the condition, but they may be more or less severely affected than their parent. Sometimes a person may have a gene variant for an autosomal dominant condition and show no signs or symptoms of the condition.^[1]

Last updated: 4/30/2021

Diagnosis Diagnosis

Variegate porphyria is diagnosed based on the symptoms, clinical examination and blood, urine and stool testing. The diagnosis may be confirmed by the results of genetic testing.^[1]^[2]

Last updated: 4/2/2021

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.

Treatment Treatment

Treatment of variegate porphyria is focused on managing the symptoms and avoiding acute attacks. Medications and hospitalization may be necessary for acute attacks to help manage the pain and other neurological symptoms.

Attacks may 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.^[1]^[2]

Specialists involved in the care of someone with variegate porphyria may include:

Hematologist
Dermatologist
Pain management specialist
Gastroenterologist
Neurologist

Last updated: 4/2/2021

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.

Find a Specialist Find a Specialist

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

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from MedlinePlus Genetics.

Related Diseases Related Diseases

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 Research

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.

Patient Registry

RDCRN- Porphyria Consortium Contact Registry (RDCRN Porphyria Consortium Contact Registry)
E-mail: RDCRNContactRegistry@epi.usf.edu
Website: https://www.rarediseasesnetwork.org/cms/porphyrias/registry

Organizations Organizations

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

American Porphyria Foundation
4915 St. Elmo Avenue
Suite 105
Bethesda, MD 20814
Toll-free: 1-866-273-3635
Telephone: +1-301-347-7166
Fax: +1-301-312-8719
E-mail: porphyrus@porphyriafoundation.com
Website: https://porphyriafoundation.org/

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

American Association for the Study of Liver Diseases
1001 North Fairfax, 4th floor
Alexandria, VA 22314
Telephone: 703–299–9766
Fax: 703–299–9622
E-mail: aasld@aasld.org
Website: http://www.aasld.org/
American Liver Foundation
39 Broadway, Suite 2700
New York, NY 10006
Toll-free: +1-800-465-4837 (Helpline)
Telephone: +1-212-668-1000
E-mail: https://liverfoundation.org/for-patients/contact-us/
Website: https://liverfoundation.org/
European Porphyria Network (EPNET)
E-mail: https://porphyria.eu/en/contact
Website: https://porphyria.eu/en

Do you know of an organization? We want to hear from you.

Living With Living With

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.

Learn More Learn More

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

MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
Genetics Home Reference (GHR) contains information on Variegate porphyria. This website is maintained by the National Library of Medicine.
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.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

Have a question? Contact a GARD Information Specialist.

References References

Singal AK, Anderson KR. Variegate Porphyria. GeneReviews. Updated Dec 2019; https://www.ncbi.nlm.nih.gov/books/NBK121283/.
Stotzel U, Doss MO, Schuppan D. Clinical guide and update on porphyrias. Gastroenterology. Aug 2019; 157(2):365-381. https://pubmed.ncbi.nlm.nih.gov/31085196.
Kothadia JP, LaFreniere K, Shah JM. Acute Hepatic Porphyria. StatPearls. Mar 2021; https://pubmed.ncbi.nlm.nih.gov/30725863.
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.