Porphyria, Hereditary Coproporphyria
Synonyms of Porphyria, Hereditary Coproporphyria
- Porphyria Hepatica, Coproporphyria
- No subdivisions found.
Hereditary Coproporphyria is an autosomal dominant form of hepatic porphyria that is very similar to Acute Intermittent Porphyria, although it is usually a less severe disease. It is caused by an enzyme deficiency. Some patients develop skin photosensitivity, and must avoid sunlight. The diagnosis is established by finding excess coproporphyrin in urine and stool (other types of porphyrins show little or no increase). Urinary ALA and PBG are increased during acute attacks, but may become normal on recovery.
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.
The large amount of coproporphyrin present in Hereditary Coproporphyria (HCP) makes the patient sensitive to sunlight, but skin disease is rarely severe in this type or porphyria. Clinically, it resembles variegate porphyria and acute intermittent porphyria. Symptoms may include abdominal pain, arm and/or leg pain, generalized weakness, vomiting, confusion, constipation, increased heart rate, fluctuating blood pressure, urinary retention, psychosis, hallucinations, and seizures. The muscle weakness may progress to respiratory paralysis, necessitating artificial respiration.
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 HCP, relatives should be examined as well. Latent cases so identified can then avoid agents known to cause attacks.
Hereditary Coproporphyria is a genetic, non-x-linked disorder inherited as an autosomal dominant trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, 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 other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.
The gene that is responsible for regulating the production of the enzyme Coproporphyrinogen Oxidase has been located on the long arm (q) of chromosome 3 (3q12). Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males, and two X chromosomes for females. Each chromosome has a short arm designated as "p" and a long arm identified by the letter "q".
Drugs such as barbiturates, tranquilizers, anticonvulsants, and estrogens may precipitate attacks.
Environmental factors may include drugs, chemicals, diet and sun exposure. Depending on the type of porphyria, these factors can greatly influence the severity of symptoms.
Because all porphyrias are uncommon, it is very unlikely that more than one type will occur in the same family, or that someone with one type of porphyria will go on to develop another.
Hereditary Coproporphyria may have its onset at any age, and may affect males and females in equal numbers. It is the least common of the "hepatic" porphyrias.
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 type or 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 this type of Porphyria. Increased porphyrins also may be found in plasma, urine, feces, 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.
Variegate Porphyria (VP) is a hereditary type of Porphyria due to an inborn error of metabolism. Precipitating or aggravating factors may include exposure to barbiturates, sulfonamides, general anesthetics, excessive amounts of ethanol, 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.
Panhematin (hemin for injection), a drug formerly known as Hematin, is very potent in suppressing acute attacks of porphyria. It is an enzyme inhibitor derived from processed red blood cells. A sterile powder, it is suitable for intravenous administration after reconstitution. Because of its potency, Panhematin is usually given after a trial of glucose therapy has not produced the desired results. It is manufactured by Abbott Laboratories.
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 was 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.
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:
Ewing Hall (J-09)
University of Texas Medical Branch
700 Strand St.
Galveston, TX 77555
The Orphan product Hemin and Zinc Mesoporphyrin (HEMEX) is being used for treatment of Acute Prophyric Syndromes. For more information, contact:
Herbert L. Bonkovsky, MD
University of Massachusetts
Worchester, MA 01655
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
Organizations related to Porphyria, Hereditary Coproporphyria
A Molecular Defect in Coproporphyrinogen Oxidase Gene Causing Harderoporphyria, A Variant Form of Hereditary Coproporphyria. J. Lamoril et al.; Hum Molec Genet (1995; 4). Pp. 275-78.
Localization of the Human Coproporphyrinogen Oxidase Gene to Chromosome Band 3q12. V. Cacheux et al.; Hum Genet (1994; 94). Pp. 557-59.
Homozygous Hereditary Coproporphyria Caused by an Arginine to Tryptophane Substitution in Coproporphyrinogen Oxidase and Common Intragenic Polymorphisms. P. Martasek et al.; Hum Molec Genet (1994; 3). Pp. 477-80.
American Porphyria Foundation brochure, "Common Questions About Porphyria."
FROM THE INTERNET
Online Mendelian Inheritance in Man (OMIM). Victor A. McKusick, Editor; Johns Hopkins University, Last Edit Date 4/4/95, Entry Number 121300.
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