Rare Gastroenterology News

Disease Profile

Variegate porphyria

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Adolescent

ICD-10

E80.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Porphyria variegate; VP; Porphyria, South African type;

Categories

Congenital and Genetic Diseases; Kidney and Urinary Diseases; Metabolic disorders;

Summary

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]

Symptoms

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] 

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.

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

Cause

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]

Diagnosis

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.

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

    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]

    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.

      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

        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

            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.

                References

                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.

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