$Unique_ID{BRK04132} $Pretitle{} $Title{Porphyria, Variegate} $Subject{Porphyria Variegate Porphyria VP Porphyria Cutanea Tarda Hereditaria Mixed Hepatic Porphyria South African Genetic Porphyria Porphyria Hepatica} $Volume{} $Log{} Copyright (C) 1987, 1988, 1990, 1991, 1993 National Organization for Rare Disorders, Inc. 324: Porphyria, Variegate ** IMPORTANT ** It is possible the main title of the article (Variegate Porphyria) is not the name you expected. Please check the SYNONYMS listing to find the alternate names and disorder subdivisions covered by this article. Synonyms Porphyria VP Porphyria Cutanea Tarda Hereditaria Mixed Hepatic Porphyria South African Genetic Porphyria Porphyria Hepatica General Discussion ** REMINDER ** The information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Variegate Porphyria (VP), a form of hepatic porphyria, is most common in the South African white population and is much less frequent elsewhere. It is an autosomal dominant disorder and may produce acute attacks (as in acute intermittent porphyria) as well as skin photosensitivity. This form of porphyria is also due to an enzyme deficiency. The diagnosis may be made by finding excess coproporphyrin in urine and both coproporphyrin and protoporphyrin in feces. In patients with photosensitive skin changes alone, it is important to distinguish Variegate Porphyria or hereditary coproporphyria (HCP) from porphyria cutanea tarda (PCT), because treatment by phlebotomy or low-dose chloroquine is not successful in VP and HCP. Acute attacks are managed and may be prevented as in AIP. The Porphyrias are a group of at least seven disorders. The common feature in all porphyrias is the excess accumulation in the body of "porphyrins" or "porphyrin precursors." These are natural chemicals that normally do not accumulate in the body. Precisely which one of these porphyrin chemicals builds up depends upon the type of porphyria that a patient has. Porphyrias can also be classified into two groups: the "hepatic" and "erythropoietic" types. Porphyrins and related substances originate in excess amounts from the liver in the hepatic types, and mostly from the bone marrow in the erythropoietic types. The porphyrias with skin manifestations are sometimes called "cutaneous porphyrias." The "acute porphyrias" are characterized by sudden attacks of pain and other neurological manifestations. These "acute symptoms can be both rapidly-appearing and severe. An individual may be considered in a "latent" condition if he or she has the characteristic enzyme deficiency, but has never developed symptoms. There can be a wide spectrum of severity between the "latent" and "active" cases of any particular type of this disorder. The symptoms and treatments of the different types of porphyrias are not the same. For more information on the other types of porphyria, choose "porphyria" as your search term in the Rare Disease Database. Symptoms Variegate Porphyria shows no symptoms during the latent phase of the disorder. During an acute attack, a patient may experience abdominal colic, severe vomiting, or sweating. The symptoms of porphyria generally arise from effects on the nervous system and/or the skin. Sometimes, the cause of the nervous system symptoms is not clear, and proper diagnosis is delayed. Skin manifestations can include burning, blistering and scarring of sun-exposed areas. Porphyria Cutanea Tarda is the only type of porphyria that can be either acquired or inherited. All other types of Porphyria are caused by genetic factors. Environmental factors such as drugs, chemicals, diet and sun exposure can, depending on the type of the disorder, greatly influence the severity of symptoms. The terms "porphyrin" and "porphyria" are derived from the Greek word "porphyrus," meaning purple. Urine from some porphyria patients may be reddish in color due to the presence of excess porphyrins and related substances, and the urine may darken after being exposed to the light. Because this disease can mimic a host of other more common conditions, its presence is often not suspected. On the other hand, the diagnosis of this and other types of porphyria is sometimes made incorrectly in patients who do not have porphyria, particularly if improper laboratory tests are carried out. The finding of increased levels of delta-aminolevulinic acid (ALA) in urine establishes that one of the "acute" porphyrias is present. When a patient is diagnosed as having VP, relatives should be examined as well. Latent cases so identified can then avoid agents known to cause attacks. Causes Variegate Porphyria (VP) is a hereditary, non-x-linked dominant disorder, due to an inborn metabolic error (a deficiency of protoporphyrinogen oxidase). Precipitating factors may include exposure to barbiturates, sulfonamides, general anesthetics, excessive amounts of alcohol, and/or estrogens. Human traits including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother. In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the normal gene and resulting in appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child. Environmental factors that can precipitate attacks of Variegate Porphyria may include drugs, chemicals, diet and sun exposure. Depending on the type of porphyria, these factors can greatly influence the severity of symptoms. Affected Population Variegate Porphyria (VP) may begin between the ages of ten to thirty years. It is particularly common in the white population of South Africa, and may affect males and females in equal numbers. Related Disorders The Porphyrias are a group of related disorders. For more information on each of the following types of the disease, choose "porphyria" as your search term in the Rare Disease Database. ALA-D Porphyria is a recently described form of acute porphyria inherited as an autosomal recessive trait. It is apparently extremely rare. There is a deficiency of the enzyme delta-aminolevulinic acid dehydratase (ALA-D) and increased excretion of ALA in the urine of patients with this form of porphyria. Acute Intermittent Porphyria is a hereditary, possibly metabolic, usually asymptomatic disorder (latent). It may possibly be provoked into active disease by the administration of certain drugs, notably barbiturates, sulfonamides, and estrogenic compounds. Congenital Erythropoietic Porphyria (CEP) is a hereditary disorder due to an inborn error of metabolism, and manifested in infancy. Faulty conversion of the enzyme PBG to uroporphyrinogen in erythroid cells of bone marrow, and red blood cells leads to of this type of Porphyria. Increased porphyrins also may be found in plasma, urine and feces. Porphyrins are also deposited in the teeth and bones. Porphyria Cutanea Tarda (PCT) can be either an acquired or inherited type of Porphyria. It may become acute due to exposure to chronic alcoholism, barbiturates or other chemicals, cirrhosis of the liver, or a hepatic tumor. It may also stem from a nutritional disorder. Hereditary Coproporphyria (HCP) is a latent type of Porphyria with attacks usually precipitated by exposure to drugs such as barbiturates, tranquilizers, anticonvulsants, and estrogens. Erythropoietic Protoporphyria (EPP) is a hereditary type of Porphyria marked by an accumulation of protoporphyrin in the bone marrow, red blood cells and sometimes the liver. Excess protoporphyrin is excreted by the liver into the bile, which in turn enters the intestine and is excreted in the feces. There are no urinary abnormalities. The diagnosis is established by finding increased protoporphyrin in red blood cells, plasma and feces. Therapies: Standard The orphan drug Hematin (an intravenous drug) is very potent in suppressing acute attacks of the disease. It is usually given only after a trial of glucose therapy. Attention should be given to salt and water balance during treatment. Many types of drugs such as aspirin and certain antibiotics are believed to be safe in patients with some types of porphyria. Recommendations about drugs for certain types of the disorder are based on experience with the porphyria patients in whom attacks have been caused by drugs and by tests in animals. Since many commonly used drugs have not been tested, they should be avoided if at all possible. If a question of drug safety arises, a physician or medical center specializing in porphyria should be contacted. A list of these institutions may be procured from the American Porphyria Foundation (see Resources). Pregnancy is tolerated much better than formerly believed. Many patients have a few reservations about family planning. For those who do, genetic counseling may be useful. Wearing a Medic Alert bracelet is advisable in patients who have had attacks, but is probably not warranted in most latent cases. Therapies: Investigational New treatments for several types of porphyria are under investigation. For the most updated information on research, please contact the organizations listed in the Resources section. Dr. Karl E. Anderson of the University of Texas Medical Branch, Galveston, TX, 77550, has received orphan drug designation for Histrelin, a drug to treat various types of Porphyria. Research is underway on the Finnish product Normasang (heme arginate). Dr. Karl Anderson of The University of Texas Medical Branch will be directing clinical studies in the United States. Patients are needed to participate in this research. People interested in this study should have their physician contact: Dr. Karl Anderson Ewing Hall (J-09) University of Texas Medical Branch 700 Strand St. Galveston, TX 77555 (409) 772-4661 This disease entry is based upon medical information available through January 1993. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Variegate Porphyria, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 American Porphyria Foundation P.O. Box 22712 Houston, TX 77227 (713) 266-9617 Porphyria Support Group 4 Eve Road Leytonstone, London, England E11 3JE Tel: 01-519-7868 National Digestive Diseases Information Clearinghouse Box NDDIC Bethesda, MD 20892 (301) 468-2344 For information on genetics and genetic counseling referrals, please contact: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 References American Porphyria Foundation brochure, "Common Questions About Porphyria."